DNSP-11

updated

DNSP-11 is an 11-amino-acid peptide derived from the proregion of the GDNF proprotein, studied by one group for roughly 15 years in cells, rats and Rhesus macaques. No controlled human study exists, and a PubMed search on 9 October 2026 for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records. Every in vivo route used was direct brain injection or intranasal delivery.

GDNF proprotein-derived neuropeptide

  • DNSP-11 is an 11-amino-acid amidated peptide from the proregion of the glial cell line-derived neurotrophic factor (GDNF) proprotein; PubChem returned no compound record for it on 9 October 2026.
  • In rats, a single injection into the substantia nigra increased resting dopamine and its metabolites for up to 28 days, and in a 6-hydroxydopamine rat model of Parkinson disease it improved apomorphine-induced rotational behavior.
  • A follow-up found no significant change in evoked dopamine release at 4 weeks by microdialysis and no change in spontaneous locomotor activity.
  • Awake Rhesus macaques given repeated intranasal DNSP-11 with dose escalation over 10 weeks showed neurochemical signs of bilateral striatal target engagement without observable adverse behavioral effects or weight loss, in a methods study that describes itself as proof of concept.
  • A PubMed search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records on 9 October 2026, and a ClinicalTrials.gov query for DNSP-11 returned no studies.
  • Every in vivo route used was direct brain injection or intranasal delivery; no subcutaneous or intramuscular study appears in the records reviewed.

What is DNSP-11, and is it approved for anything?

DNSP-11 is an 11-amino-acid amidated peptide from the proregion of the GDNF proprotein. No approval for any use appears in the records reviewed, and PubChem returned no compound record for it on 9 October 2026.

DNSP-11, dopamine neuron stimulating peptide-11, is an 11-amino-acid amidated peptide from the proregion of the glial cell line-derived neurotrophic factor (GDNF) proprotein. It is hypothesized to be produced by endoproteolytic processing of proGDNF, and it is one of three such peptides studied by the same group, alongside a 5-mer (DNSP-5) and a 17-mer (DNSP-17).

PubChem returned no compound record on 9 October 2026 for DNSP-11, DNSP-11 peptide or dopamine neuron stimulating peptide-11, so no formula, molecular weight or CAS number is printed here.

A ClinicalTrials.gov query for DNSP-11 on 9 October 2026 returned no studies. A PubMed search for DNSP-11 or dopamine neuron stimulating peptide returned 10 records, all rodent, cell, primate, antibody or review work plus two unrelated papers. No approval for any use appears in the records reviewed.

Founding report: neurons and cell lines in vitro, single nigral injection in rats

Animal study

Bradley LH et al. PLoS One. 2010;5(3):e9752. PMID 20305789.

DNSP-11, dopamine neuron stimulating peptide-11, is an 11-amino-acid amidated peptide from the proregion of the glial cell line-derived neurotrophic factor (GDNF) proprotein, hypothesized to be produced by endoproteolytic processing of proGDNF. In vitro it supported survival of fetal mesencephalic neurons, increasing both surviving cell number and neuritic outgrowth, and in MN9D cells it protected against 6-hydroxydopamine-induced cell death, significantly decreasing TUNEL-positive cells and caspase-3 activity. In vivo, a single injection into the substantia nigra of normal adult rats was taken up rapidly into neurons and increased resting dopamine and its metabolites for up to 28 days; in a rat model of Parkinson disease it significantly improved apomorphine-induced rotational behavior and increased nigral dopamine and metabolite tissue levels. Unlike GDNF, it blocked staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing release of cytochrome c from mitochondria.

Participants / model
Rat fetal mesencephalic neurons, MN9D and B65 cell lines, normal adult rats, 6-hydroxydopamine lesioned rats
Treatment
Direct injection into the substantia nigra in vivo; media exposure in vitro
Follow-up
Resting dopamine increases followed for up to 28 days
Study design
Original preclinical study
Funding
not stated in the source

The mitochondrial finding is one cell-line observation about cytochrome c release, not a measure of mitochondrial function in an animal or a person. DNSP-11 is one of three peptides studied by the same group, alongside a 5-mer (DNSP-5) and a 17-mer (DNSP-17).

Read the original source
Searches, 9 October 2026: no human data and no mood studies for DNSP-11

PubMed search record

PubMed search run on 9 October 2026: DNSP-11 OR dopamine neuron stimulating peptide, 10 records. A second PubMed search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records. A ClinicalTrials.gov query for DNSP-11 run the same day.

The search for DNSP-11 or dopamine neuron stimulating peptide returned 10 records: the rodent, cell, primate, antibody and review work described on this page, plus two unrelated papers on amylin isoforms and GDNF isoforms. A search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records, and a ClinicalTrials.gov query for DNSP-11 returned no studies. The records reviewed contain no human dose, no human pharmacokinetics, no human safety data, no clinical trial and no study of any kind on mood, depression or anxiety. Every in vivo route used was direct brain injection or intranasal delivery; no subcutaneous or intramuscular study appears. PubChem returned no compound record for DNSP-11 on 9 October 2026.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

What have cell, rat and macaque studies found?

In cultured neurons and cell lines DNSP-11 supported survival, and in rats it raised dopamine measures after a nigral injection or repeated intranasal dosing, with mixed results in one follow-up. A 10-week macaque study reported target engagement and no observable adverse behavioral effects. No study gave it to a person.

In vitro, DNSP-11 supported survival of fetal mesencephalic neurons, increasing both surviving cell number and neuritic outgrowth, and in MN9D cells it protected against 6-hydroxydopamine-induced cell death, significantly decreasing TUNEL-positive cells and caspase-3 activity.

In vivo, a single injection into the substantia nigra of normal adult rats was taken up rapidly into neurons and increased resting dopamine and its metabolites for up to 28 days. In a rat model of Parkinson disease it significantly improved apomorphine-induced rotational behavior and increased nigral dopamine and metabolite tissue levels.

A follow-up gave mixed results. After a single nigral treatment there were no significant changes in potassium- or D-amphetamine-evoked dopamine release at 4 weeks by microdialysis. Chronoamperometry found potassium-evoked dopamine release increased in specific striatal subregions at 2 weeks, but spontaneous locomotor activity was unchanged. The effect was regional and transient, and it did not change behavior.

Normal rats given varying intranasal doses for 3 weeks showed a significant increase in dopamine turnover in both striatum and substantia nigra at 300 micrograms. In unilateral 6-hydroxydopamine lesioned rats, repeated intranasal dosing decreased d-amphetamine-induced rotation at 2 weeks, decreased dopamine turnover in the lesioned striatum and increased sparing of tyrosine hydroxylase positive neurons in a sub-region of the lesioned substantia nigra pars compacta. Radiolabeled tracer was distributed diffusely through the brain as quickly as 30 minutes after a single intranasal dose.

The largest animal step is a methods study in awake Rhesus macaques, including MPTP-treated animals, given repeated intranasal DNSP-11 with dose escalation over 10 weeks. The authors reported bilateral striatal target engagement based on neurochemical changes in dopamine metabolites, without observable adverse behavioral effects or weight loss. The paper describes itself as proof of concept and reports target engagement and tolerability, not a clinical or behavioral benefit.

Founding report: neurons and cell lines in vitro, single nigral injection in rats

Animal study

Bradley LH et al. PLoS One. 2010;5(3):e9752. PMID 20305789.

DNSP-11, dopamine neuron stimulating peptide-11, is an 11-amino-acid amidated peptide from the proregion of the glial cell line-derived neurotrophic factor (GDNF) proprotein, hypothesized to be produced by endoproteolytic processing of proGDNF. In vitro it supported survival of fetal mesencephalic neurons, increasing both surviving cell number and neuritic outgrowth, and in MN9D cells it protected against 6-hydroxydopamine-induced cell death, significantly decreasing TUNEL-positive cells and caspase-3 activity. In vivo, a single injection into the substantia nigra of normal adult rats was taken up rapidly into neurons and increased resting dopamine and its metabolites for up to 28 days; in a rat model of Parkinson disease it significantly improved apomorphine-induced rotational behavior and increased nigral dopamine and metabolite tissue levels. Unlike GDNF, it blocked staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing release of cytochrome c from mitochondria.

Participants / model
Rat fetal mesencephalic neurons, MN9D and B65 cell lines, normal adult rats, 6-hydroxydopamine lesioned rats
Treatment
Direct injection into the substantia nigra in vivo; media exposure in vitro
Follow-up
Resting dopamine increases followed for up to 28 days
Study design
Original preclinical study
Funding
not stated in the source

The mitochondrial finding is one cell-line observation about cytochrome c release, not a measure of mitochondrial function in an animal or a person. DNSP-11 is one of three peptides studied by the same group, alongside a 5-mer (DNSP-5) and a 17-mer (DNSP-17).

Read the original source
Follow-up: mixed results after a single nigral injection in rats

Animal study

Fuqua JL et al. Peptides. 2014;54:1-8. PMID 24406899.

After a single DNSP-11 treatment to the rat substantia nigra, there were no significant changes in potassium- or D-amphetamine-evoked dopamine release at 4 weeks by microdialysis. High-speed chronoamperometry found potassium-evoked dopamine release increased in specific striatal subregions at 2 weeks, but spontaneous locomotor activity was unchanged. In MN9D cells a single treatment produced ERK1/2 phosphorylation.

Participants / model
Normal adult rats; MN9D dopaminergic cell line
Treatment
Single injection into the substantia nigra
Follow-up
2 and 4 weeks after the injection
Study design
Original preclinical study
Funding
not stated in the source

The effect is regional and transient in this experiment, and it did not change behavior.

Read the original source
Intranasal in rats: 3 weeks of repeated dosing, dopamine turnover and lesion models

Animal study

Stenslik MJ et al. J Neurosci Methods. 2015;251:120-9. PMID 25999268.

Normal rats given varying intranasal doses for 3 weeks showed a significant increase in dopamine turnover in both striatum and substantia nigra at 300 micrograms. In unilateral 6-hydroxydopamine lesioned rats, repeated intranasal dosing produced a significant decrease in d-amphetamine-induced rotation at 2 weeks, decreased dopamine turnover in the lesioned striatum, and increased sparing of tyrosine hydroxylase positive neurons in a specific sub-region of the lesioned substantia nigra pars compacta. Radiolabeled tracer was distributed diffusely through the brain, including striatum and substantia nigra, as quickly as 30 minutes after a single intranasal dose.

Participants / model
Normal and unilateral 6-hydroxydopamine lesioned rats
Treatment
Repeated intranasal delivery under light sedation
Follow-up
3 weeks
Study design
Original preclinical study
Funding
not stated in the source

Rat results. The 300 microgram figure is the amount at which one dopamine turnover effect was seen in this study, not a recommended amount.

Read the original source
Rhesus macaques: 10 weeks of repeated intranasal dosing, target engagement and tolerability

Animal study

Stenslik MJ et al. J Neurosci Methods. 2018;303:30-40. PMID 29614295.

Awake Rhesus macaques received repeated intranasal DNSP-11 with dose escalation over 10 weeks. The authors reported bilateral striatal target engagement based on neurochemical changes in dopamine metabolites, without observable adverse behavioral effects or weight loss, and a single radiolabeled dose showed diffuse rostral to caudal brain distribution including the striatum.

Participants / model
Awake Rhesus macaques, including MPTP-treated animals
Treatment
Repeated intranasal delivery with dose escalation
Follow-up
10 weeks
Study design
Preclinical methods study that describes itself as proof of concept
Funding
not stated in the source

The paper reports target engagement and tolerability, not a clinical or behavioral benefit.

Read the original source

By which routes were animals dosed?

Only direct injection into the brain (the substantia nigra) or intranasal delivery. No subcutaneous or intramuscular study appears in the records reviewed, so the results do not describe injection into the body.

Every in vivo route used was direct injection into the substantia nigra or intranasal delivery, in rats and in macaques. No subcutaneous or intramuscular study appears in the records reviewed.

Results from a nigral injection or from repeated intranasal delivery do not carry over to a different route, and no study tested a different route.

Searches, 9 October 2026: no human data and no mood studies for DNSP-11

PubMed search record

PubMed search run on 9 October 2026: DNSP-11 OR dopamine neuron stimulating peptide, 10 records. A second PubMed search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records. A ClinicalTrials.gov query for DNSP-11 run the same day.

The search for DNSP-11 or dopamine neuron stimulating peptide returned 10 records: the rodent, cell, primate, antibody and review work described on this page, plus two unrelated papers on amylin isoforms and GDNF isoforms. A search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records, and a ClinicalTrials.gov query for DNSP-11 returned no studies. The records reviewed contain no human dose, no human pharmacokinetics, no human safety data, no clinical trial and no study of any kind on mood, depression or anxiety. Every in vivo route used was direct brain injection or intranasal delivery; no subcutaneous or intramuscular study appears. PubChem returned no compound record for DNSP-11 on 9 October 2026.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source
Founding report: neurons and cell lines in vitro, single nigral injection in rats

Animal study

Bradley LH et al. PLoS One. 2010;5(3):e9752. PMID 20305789.

DNSP-11, dopamine neuron stimulating peptide-11, is an 11-amino-acid amidated peptide from the proregion of the glial cell line-derived neurotrophic factor (GDNF) proprotein, hypothesized to be produced by endoproteolytic processing of proGDNF. In vitro it supported survival of fetal mesencephalic neurons, increasing both surviving cell number and neuritic outgrowth, and in MN9D cells it protected against 6-hydroxydopamine-induced cell death, significantly decreasing TUNEL-positive cells and caspase-3 activity. In vivo, a single injection into the substantia nigra of normal adult rats was taken up rapidly into neurons and increased resting dopamine and its metabolites for up to 28 days; in a rat model of Parkinson disease it significantly improved apomorphine-induced rotational behavior and increased nigral dopamine and metabolite tissue levels. Unlike GDNF, it blocked staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing release of cytochrome c from mitochondria.

Participants / model
Rat fetal mesencephalic neurons, MN9D and B65 cell lines, normal adult rats, 6-hydroxydopamine lesioned rats
Treatment
Direct injection into the substantia nigra in vivo; media exposure in vitro
Follow-up
Resting dopamine increases followed for up to 28 days
Study design
Original preclinical study
Funding
not stated in the source

The mitochondrial finding is one cell-line observation about cytochrome c release, not a measure of mitochondrial function in an animal or a person. DNSP-11 is one of three peptides studied by the same group, alongside a 5-mer (DNSP-5) and a 17-mer (DNSP-17).

Read the original source
Intranasal in rats: 3 weeks of repeated dosing, dopamine turnover and lesion models

Animal study

Stenslik MJ et al. J Neurosci Methods. 2015;251:120-9. PMID 25999268.

Normal rats given varying intranasal doses for 3 weeks showed a significant increase in dopamine turnover in both striatum and substantia nigra at 300 micrograms. In unilateral 6-hydroxydopamine lesioned rats, repeated intranasal dosing produced a significant decrease in d-amphetamine-induced rotation at 2 weeks, decreased dopamine turnover in the lesioned striatum, and increased sparing of tyrosine hydroxylase positive neurons in a specific sub-region of the lesioned substantia nigra pars compacta. Radiolabeled tracer was distributed diffusely through the brain, including striatum and substantia nigra, as quickly as 30 minutes after a single intranasal dose.

Participants / model
Normal and unilateral 6-hydroxydopamine lesioned rats
Treatment
Repeated intranasal delivery under light sedation
Follow-up
3 weeks
Study design
Original preclinical study
Funding
not stated in the source

Rat results. The 300 microgram figure is the amount at which one dopamine turnover effect was seen in this study, not a recommended amount.

Read the original source
Rhesus macaques: 10 weeks of repeated intranasal dosing, target engagement and tolerability

Animal study

Stenslik MJ et al. J Neurosci Methods. 2018;303:30-40. PMID 29614295.

Awake Rhesus macaques received repeated intranasal DNSP-11 with dose escalation over 10 weeks. The authors reported bilateral striatal target engagement based on neurochemical changes in dopamine metabolites, without observable adverse behavioral effects or weight loss, and a single radiolabeled dose showed diffuse rostral to caudal brain distribution including the striatum.

Participants / model
Awake Rhesus macaques, including MPTP-treated animals
Treatment
Repeated intranasal delivery with dose escalation
Follow-up
10 weeks
Study design
Preclinical methods study that describes itself as proof of concept
Funding
not stated in the source

The paper reports target engagement and tolerability, not a clinical or behavioral benefit.

Read the original source

Do the mood, mitochondrial and neuroprotection claims hold up?

Not as sold. Neuroprotection is supported only as dopaminergic neuron protection in cultured cells and lesioned rats, the mitochondrial claim is one cell-line observation, and no study of any kind addresses mood. No study combined DNSP-11 with any other compound.

Sellers describe DNSP-11 for mood support, mitochondrial function and neuroprotection, used alongside semax, selank or FGL.

Neuroprotection is supported only as dopaminergic neuron protection in cultured cells and in 6-hydroxydopamine lesioned rats, not as general neuroprotection in people.

The mitochondrial claim rests on one observation: unlike GDNF, DNSP-11 blocked staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing release of cytochrome c from mitochondria. That is a single cell-line observation about cytochrome c release, not a measure of mitochondrial function in an animal or a person.

The mood claim has no supporting literature. A PubMed search on 9 October 2026 for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records.

The pairing with semax, selank or FGL has no study behind it, and the page does not describe the combination as compatible or synergistic. No study in the records reviewed combined DNSP-11 with any other compound.

Founding report: neurons and cell lines in vitro, single nigral injection in rats

Animal study

Bradley LH et al. PLoS One. 2010;5(3):e9752. PMID 20305789.

DNSP-11, dopamine neuron stimulating peptide-11, is an 11-amino-acid amidated peptide from the proregion of the glial cell line-derived neurotrophic factor (GDNF) proprotein, hypothesized to be produced by endoproteolytic processing of proGDNF. In vitro it supported survival of fetal mesencephalic neurons, increasing both surviving cell number and neuritic outgrowth, and in MN9D cells it protected against 6-hydroxydopamine-induced cell death, significantly decreasing TUNEL-positive cells and caspase-3 activity. In vivo, a single injection into the substantia nigra of normal adult rats was taken up rapidly into neurons and increased resting dopamine and its metabolites for up to 28 days; in a rat model of Parkinson disease it significantly improved apomorphine-induced rotational behavior and increased nigral dopamine and metabolite tissue levels. Unlike GDNF, it blocked staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing release of cytochrome c from mitochondria.

Participants / model
Rat fetal mesencephalic neurons, MN9D and B65 cell lines, normal adult rats, 6-hydroxydopamine lesioned rats
Treatment
Direct injection into the substantia nigra in vivo; media exposure in vitro
Follow-up
Resting dopamine increases followed for up to 28 days
Study design
Original preclinical study
Funding
not stated in the source

The mitochondrial finding is one cell-line observation about cytochrome c release, not a measure of mitochondrial function in an animal or a person. DNSP-11 is one of three peptides studied by the same group, alongside a 5-mer (DNSP-5) and a 17-mer (DNSP-17).

Read the original source
Searches, 9 October 2026: no human data and no mood studies for DNSP-11

PubMed search record

PubMed search run on 9 October 2026: DNSP-11 OR dopamine neuron stimulating peptide, 10 records. A second PubMed search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records. A ClinicalTrials.gov query for DNSP-11 run the same day.

The search for DNSP-11 or dopamine neuron stimulating peptide returned 10 records: the rodent, cell, primate, antibody and review work described on this page, plus two unrelated papers on amylin isoforms and GDNF isoforms. A search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records, and a ClinicalTrials.gov query for DNSP-11 returned no studies. The records reviewed contain no human dose, no human pharmacokinetics, no human safety data, no clinical trial and no study of any kind on mood, depression or anxiety. Every in vivo route used was direct brain injection or intranasal delivery; no subcutaneous or intramuscular study appears. PubChem returned no compound record for DNSP-11 on 9 October 2026.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

How does DNSP-11 work?

The sources describe dopaminergic effects and cell protection but no confirmed receptor mechanism. In cells DNSP-11 produced ERK1/2 phosphorylation and prevented cytochrome c release from mitochondria, and in rats and macaques it changed dopamine and dopamine metabolite measures.

DNSP-11 is hypothesized to be produced by endoproteolytic processing of proGDNF. In MN9D cells a single treatment produced ERK1/2 phosphorylation, and in nutrient-deprived B65 cells its protective effects included preventing release of cytochrome c from mitochondria. The sources reviewed do not describe a receptor through which it acts.

In rats it increased resting dopamine and its metabolites for up to 28 days after a single nigral injection, and repeated intranasal dosing raised dopamine turnover at 300 micrograms. In macaques the authors inferred striatal target engagement from changes in dopamine metabolites.

In bench tests, all three GDNF-derived peptides were soluble and stable for one month across a range of storage and experimental conditions. DNSP-17 bound heparin as tightly as GDNF, while DNSP-5 and DNSP-11 did not. This is bench stability, not a shelf-life or reconstitution claim for a vendor product.

No half-life or other pharmacokinetic parameter is published for any species. The only exposure data are radiolabeled brain distribution after a single intranasal dose.

Founding report: neurons and cell lines in vitro, single nigral injection in rats

Animal study

Bradley LH et al. PLoS One. 2010;5(3):e9752. PMID 20305789.

DNSP-11, dopamine neuron stimulating peptide-11, is an 11-amino-acid amidated peptide from the proregion of the glial cell line-derived neurotrophic factor (GDNF) proprotein, hypothesized to be produced by endoproteolytic processing of proGDNF. In vitro it supported survival of fetal mesencephalic neurons, increasing both surviving cell number and neuritic outgrowth, and in MN9D cells it protected against 6-hydroxydopamine-induced cell death, significantly decreasing TUNEL-positive cells and caspase-3 activity. In vivo, a single injection into the substantia nigra of normal adult rats was taken up rapidly into neurons and increased resting dopamine and its metabolites for up to 28 days; in a rat model of Parkinson disease it significantly improved apomorphine-induced rotational behavior and increased nigral dopamine and metabolite tissue levels. Unlike GDNF, it blocked staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing release of cytochrome c from mitochondria.

Participants / model
Rat fetal mesencephalic neurons, MN9D and B65 cell lines, normal adult rats, 6-hydroxydopamine lesioned rats
Treatment
Direct injection into the substantia nigra in vivo; media exposure in vitro
Follow-up
Resting dopamine increases followed for up to 28 days
Study design
Original preclinical study
Funding
not stated in the source

The mitochondrial finding is one cell-line observation about cytochrome c release, not a measure of mitochondrial function in an animal or a person. DNSP-11 is one of three peptides studied by the same group, alongside a 5-mer (DNSP-5) and a 17-mer (DNSP-17).

Read the original source
Follow-up: mixed results after a single nigral injection in rats

Animal study

Fuqua JL et al. Peptides. 2014;54:1-8. PMID 24406899.

After a single DNSP-11 treatment to the rat substantia nigra, there were no significant changes in potassium- or D-amphetamine-evoked dopamine release at 4 weeks by microdialysis. High-speed chronoamperometry found potassium-evoked dopamine release increased in specific striatal subregions at 2 weeks, but spontaneous locomotor activity was unchanged. In MN9D cells a single treatment produced ERK1/2 phosphorylation.

Participants / model
Normal adult rats; MN9D dopaminergic cell line
Treatment
Single injection into the substantia nigra
Follow-up
2 and 4 weeks after the injection
Study design
Original preclinical study
Funding
not stated in the source

The effect is regional and transient in this experiment, and it did not change behavior.

Read the original source
Intranasal in rats: 3 weeks of repeated dosing, dopamine turnover and lesion models

Animal study

Stenslik MJ et al. J Neurosci Methods. 2015;251:120-9. PMID 25999268.

Normal rats given varying intranasal doses for 3 weeks showed a significant increase in dopamine turnover in both striatum and substantia nigra at 300 micrograms. In unilateral 6-hydroxydopamine lesioned rats, repeated intranasal dosing produced a significant decrease in d-amphetamine-induced rotation at 2 weeks, decreased dopamine turnover in the lesioned striatum, and increased sparing of tyrosine hydroxylase positive neurons in a specific sub-region of the lesioned substantia nigra pars compacta. Radiolabeled tracer was distributed diffusely through the brain, including striatum and substantia nigra, as quickly as 30 minutes after a single intranasal dose.

Participants / model
Normal and unilateral 6-hydroxydopamine lesioned rats
Treatment
Repeated intranasal delivery under light sedation
Follow-up
3 weeks
Study design
Original preclinical study
Funding
not stated in the source

Rat results. The 300 microgram figure is the amount at which one dopamine turnover effect was seen in this study, not a recommended amount.

Read the original source
Rhesus macaques: 10 weeks of repeated intranasal dosing, target engagement and tolerability

Animal study

Stenslik MJ et al. J Neurosci Methods. 2018;303:30-40. PMID 29614295.

Awake Rhesus macaques received repeated intranasal DNSP-11 with dose escalation over 10 weeks. The authors reported bilateral striatal target engagement based on neurochemical changes in dopamine metabolites, without observable adverse behavioral effects or weight loss, and a single radiolabeled dose showed diffuse rostral to caudal brain distribution including the striatum.

Participants / model
Awake Rhesus macaques, including MPTP-treated animals
Treatment
Repeated intranasal delivery with dose escalation
Follow-up
10 weeks
Study design
Preclinical methods study that describes itself as proof of concept
Funding
not stated in the source

The paper reports target engagement and tolerability, not a clinical or behavioral benefit.

Read the original source
Bench handling: soluble, stable for one month, no tight heparin binding for DNSP-11

Cell study

Kelps KA et al. Neuropeptides. 2011;45(3):213-8. PMID 21507484.

Far-UV circular dichroism showed the three GDNF-derived peptides are soluble and act independently in vitro, and reverse phase HPLC with mass spectrometry showed all three were stable for one month across a range of storage and experimental conditions. DNSP-17 bound heparin as tightly as GDNF, while DNSP-5 and DNSP-11 did not, which the authors expected to help delivery in vivo.

Participants / model
No treated organism; peptide preparations and HEK-293 cells
Treatment
Peptide solutions under stated storage and experimental conditions
Follow-up
One month of stability testing
Study design
Original preclinical bench study
Funding
not stated in the source

This is bench stability, not a shelf-life or reconstitution claim for a vendor product.

Read the original source

What is known about the risks of DNSP-11?

Almost nothing. No human dose, pharmacokinetics or safety data exist. In macaques given repeated intranasal doses for 10 weeks the authors reported no observable adverse behavioral effects or weight loss, which is tolerability in animals and not safety in people.

The records reviewed contain no human dose, no human pharmacokinetics, no human safety data and no clinical trial for DNSP-11.

In awake Rhesus macaques given repeated intranasal DNSP-11 with dose escalation over 10 weeks, the authors reported bilateral striatal target engagement without observable adverse behavioral effects or weight loss. The paper is a methods report and describes itself as proof of concept.

All in vivo work used direct brain injection or intranasal delivery, so nothing is known about injection into the body. No half-life is published for any species, and PubChem returned no compound record, so a vial sold as DNSP-11 cannot be matched to a public chemical record by name alone.

Searches, 9 October 2026: no human data and no mood studies for DNSP-11

PubMed search record

PubMed search run on 9 October 2026: DNSP-11 OR dopamine neuron stimulating peptide, 10 records. A second PubMed search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records. A ClinicalTrials.gov query for DNSP-11 run the same day.

The search for DNSP-11 or dopamine neuron stimulating peptide returned 10 records: the rodent, cell, primate, antibody and review work described on this page, plus two unrelated papers on amylin isoforms and GDNF isoforms. A search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records, and a ClinicalTrials.gov query for DNSP-11 returned no studies. The records reviewed contain no human dose, no human pharmacokinetics, no human safety data, no clinical trial and no study of any kind on mood, depression or anxiety. Every in vivo route used was direct brain injection or intranasal delivery; no subcutaneous or intramuscular study appears. PubChem returned no compound record for DNSP-11 on 9 October 2026.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source
Rhesus macaques: 10 weeks of repeated intranasal dosing, target engagement and tolerability

Animal study

Stenslik MJ et al. J Neurosci Methods. 2018;303:30-40. PMID 29614295.

Awake Rhesus macaques received repeated intranasal DNSP-11 with dose escalation over 10 weeks. The authors reported bilateral striatal target engagement based on neurochemical changes in dopamine metabolites, without observable adverse behavioral effects or weight loss, and a single radiolabeled dose showed diffuse rostral to caudal brain distribution including the striatum.

Participants / model
Awake Rhesus macaques, including MPTP-treated animals
Treatment
Repeated intranasal delivery with dose escalation
Follow-up
10 weeks
Study design
Preclinical methods study that describes itself as proof of concept
Funding
not stated in the source

The paper reports target engagement and tolerability, not a clinical or behavioral benefit.

Read the original source
Intranasal in rats: 3 weeks of repeated dosing, dopamine turnover and lesion models

Animal study

Stenslik MJ et al. J Neurosci Methods. 2015;251:120-9. PMID 25999268.

Normal rats given varying intranasal doses for 3 weeks showed a significant increase in dopamine turnover in both striatum and substantia nigra at 300 micrograms. In unilateral 6-hydroxydopamine lesioned rats, repeated intranasal dosing produced a significant decrease in d-amphetamine-induced rotation at 2 weeks, decreased dopamine turnover in the lesioned striatum, and increased sparing of tyrosine hydroxylase positive neurons in a specific sub-region of the lesioned substantia nigra pars compacta. Radiolabeled tracer was distributed diffusely through the brain, including striatum and substantia nigra, as quickly as 30 minutes after a single intranasal dose.

Participants / model
Normal and unilateral 6-hydroxydopamine lesioned rats
Treatment
Repeated intranasal delivery under light sedation
Follow-up
3 weeks
Study design
Original preclinical study
Funding
not stated in the source

Rat results. The 300 microgram figure is the amount at which one dopamine turnover effect was seen in this study, not a recommended amount.

Read the original source

Why does DNSP-11 sit in C tier?

The animal record is coherent and includes a primate tolerability study, but it is the whole record: no human exposure, no pharmacokinetics beyond radiolabeled distribution, and no registered trial in the 16 years since the founding paper.

The published work comes from one group over roughly 15 years: a defined peptide from the GDNF propeptide region, consistent dopaminergic effects in cells and in rats, and a primate tolerability and target-engagement study. It is also the entire record. There is no human exposure, and the program has not reached a registered trial in the 16 years since the founding paper.

The follow-up work reports its own limits: the 2014 study found no change in evoked dopamine release by microdialysis at 4 weeks and no change in locomotor activity. The mood claim has no literature behind it, and the mitochondrial claim is one cell-line observation.

Founding report: neurons and cell lines in vitro, single nigral injection in rats

Animal study

Bradley LH et al. PLoS One. 2010;5(3):e9752. PMID 20305789.

DNSP-11, dopamine neuron stimulating peptide-11, is an 11-amino-acid amidated peptide from the proregion of the glial cell line-derived neurotrophic factor (GDNF) proprotein, hypothesized to be produced by endoproteolytic processing of proGDNF. In vitro it supported survival of fetal mesencephalic neurons, increasing both surviving cell number and neuritic outgrowth, and in MN9D cells it protected against 6-hydroxydopamine-induced cell death, significantly decreasing TUNEL-positive cells and caspase-3 activity. In vivo, a single injection into the substantia nigra of normal adult rats was taken up rapidly into neurons and increased resting dopamine and its metabolites for up to 28 days; in a rat model of Parkinson disease it significantly improved apomorphine-induced rotational behavior and increased nigral dopamine and metabolite tissue levels. Unlike GDNF, it blocked staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing release of cytochrome c from mitochondria.

Participants / model
Rat fetal mesencephalic neurons, MN9D and B65 cell lines, normal adult rats, 6-hydroxydopamine lesioned rats
Treatment
Direct injection into the substantia nigra in vivo; media exposure in vitro
Follow-up
Resting dopamine increases followed for up to 28 days
Study design
Original preclinical study
Funding
not stated in the source

The mitochondrial finding is one cell-line observation about cytochrome c release, not a measure of mitochondrial function in an animal or a person. DNSP-11 is one of three peptides studied by the same group, alongside a 5-mer (DNSP-5) and a 17-mer (DNSP-17).

Read the original source
Follow-up: mixed results after a single nigral injection in rats

Animal study

Fuqua JL et al. Peptides. 2014;54:1-8. PMID 24406899.

After a single DNSP-11 treatment to the rat substantia nigra, there were no significant changes in potassium- or D-amphetamine-evoked dopamine release at 4 weeks by microdialysis. High-speed chronoamperometry found potassium-evoked dopamine release increased in specific striatal subregions at 2 weeks, but spontaneous locomotor activity was unchanged. In MN9D cells a single treatment produced ERK1/2 phosphorylation.

Participants / model
Normal adult rats; MN9D dopaminergic cell line
Treatment
Single injection into the substantia nigra
Follow-up
2 and 4 weeks after the injection
Study design
Original preclinical study
Funding
not stated in the source

The effect is regional and transient in this experiment, and it did not change behavior.

Read the original source
Rhesus macaques: 10 weeks of repeated intranasal dosing, target engagement and tolerability

Animal study

Stenslik MJ et al. J Neurosci Methods. 2018;303:30-40. PMID 29614295.

Awake Rhesus macaques received repeated intranasal DNSP-11 with dose escalation over 10 weeks. The authors reported bilateral striatal target engagement based on neurochemical changes in dopamine metabolites, without observable adverse behavioral effects or weight loss, and a single radiolabeled dose showed diffuse rostral to caudal brain distribution including the striatum.

Participants / model
Awake Rhesus macaques, including MPTP-treated animals
Treatment
Repeated intranasal delivery with dose escalation
Follow-up
10 weeks
Study design
Preclinical methods study that describes itself as proof of concept
Funding
not stated in the source

The paper reports target engagement and tolerability, not a clinical or behavioral benefit.

Read the original source
Searches, 9 October 2026: no human data and no mood studies for DNSP-11

PubMed search record

PubMed search run on 9 October 2026: DNSP-11 OR dopamine neuron stimulating peptide, 10 records. A second PubMed search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records. A ClinicalTrials.gov query for DNSP-11 run the same day.

The search for DNSP-11 or dopamine neuron stimulating peptide returned 10 records: the rodent, cell, primate, antibody and review work described on this page, plus two unrelated papers on amylin isoforms and GDNF isoforms. A search for DNSP-11 with depression, mood, anxiety or antidepressant returned 0 records, and a ClinicalTrials.gov query for DNSP-11 returned no studies. The records reviewed contain no human dose, no human pharmacokinetics, no human safety data, no clinical trial and no study of any kind on mood, depression or anxiety. Every in vivo route used was direct brain injection or intranasal delivery; no subcutaneous or intramuscular study appears. PubChem returned no compound record for DNSP-11 on 9 October 2026.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

Founding report: neurons and cell lines in vitro, single nigral injection in rats

Animal study

Bradley LH et al. PLoS One. 2010;5(3):e9752. PMID 20305789.

DNSP-11, dopamine neuron stimulating peptide-11, is an 11-amino-acid amidated peptide from the proregion of the glial cell line-derived neurotrophic factor (GDNF) proprotein, hypothesized to be produced by endoproteolytic processing of proGDNF. In vitro it supported survival of fetal mesencephalic neurons, increasing both surviving cell number and neuritic outgrowth, and in MN9D cells it protected against 6-hydroxydopamine-induced cell death, significantly decreasing TUNEL-positive cells and caspase-3 activity. In vivo, a single injection into the substantia nigra of normal adult rats was taken up rapidly into neurons and increased resting dopamine and its metabolites for up to 28 days; in a rat model of Parkinson disease it significantly improved apomorphine-induced rotational behavior and increased nigral dopamine and metabolite tissue levels. Unlike GDNF, it blocked staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing release of cytochrome c from mitochondria.

Participants / model
Rat fetal mesencephalic neurons, MN9D and B65 cell lines, normal adult rats, 6-hydroxydopamine lesioned rats
Treatment
Direct injection into the substantia nigra in vivo; media exposure in vitro
Follow-up
Resting dopamine increases followed for up to 28 days
Study design
Original preclinical study
Funding
not stated in the source

The mitochondrial finding is one cell-line observation about cytochrome c release, not a measure of mitochondrial function in an animal or a person. DNSP-11 is one of three peptides studied by the same group, alongside a 5-mer (DNSP-5) and a 17-mer (DNSP-17).

Read the original source
Follow-up: mixed results after a single nigral injection in rats

Animal study

Fuqua JL et al. Peptides. 2014;54:1-8. PMID 24406899.

After a single DNSP-11 treatment to the rat substantia nigra, there were no significant changes in potassium- or D-amphetamine-evoked dopamine release at 4 weeks by microdialysis. High-speed chronoamperometry found potassium-evoked dopamine release increased in specific striatal subregions at 2 weeks, but spontaneous locomotor activity was unchanged. In MN9D cells a single treatment produced ERK1/2 phosphorylation.

Participants / model
Normal adult rats; MN9D dopaminergic cell line
Treatment
Single injection into the substantia nigra
Follow-up
2 and 4 weeks after the injection
Study design
Original preclinical study
Funding
not stated in the source

The effect is regional and transient in this experiment, and it did not change behavior.

Read the original source
Intranasal in rats: 3 weeks of repeated dosing, dopamine turnover and lesion models

Animal study

Stenslik MJ et al. J Neurosci Methods. 2015;251:120-9. PMID 25999268.

Normal rats given varying intranasal doses for 3 weeks showed a significant increase in dopamine turnover in both striatum and substantia nigra at 300 micrograms. In unilateral 6-hydroxydopamine lesioned rats, repeated intranasal dosing produced a significant decrease in d-amphetamine-induced rotation at 2 weeks, decreased dopamine turnover in the lesioned striatum, and increased sparing of tyrosine hydroxylase positive neurons in a specific sub-region of the lesioned substantia nigra pars compacta. Radiolabeled tracer was distributed diffusely through the brain, including striatum and substantia nigra, as quickly as 30 minutes after a single intranasal dose.

Participants / model
Normal and unilateral 6-hydroxydopamine lesioned rats
Treatment
Repeated intranasal delivery under light sedation
Follow-up
3 weeks
Study design
Original preclinical study
Funding
not stated in the source

Rat results. The 300 microgram figure is the amount at which one dopamine turnover effect was seen in this study, not a recommended amount.

Read the original source
Rhesus macaques: 10 weeks of repeated intranasal dosing, target engagement and tolerability

Animal study

Stenslik MJ et al. J Neurosci Methods. 2018;303:30-40. PMID 29614295.

Awake Rhesus macaques received repeated intranasal DNSP-11 with dose escalation over 10 weeks. The authors reported bilateral striatal target engagement based on neurochemical changes in dopamine metabolites, without observable adverse behavioral effects or weight loss, and a single radiolabeled dose showed diffuse rostral to caudal brain distribution including the striatum.

Participants / model
Awake Rhesus macaques, including MPTP-treated animals
Treatment
Repeated intranasal delivery with dose escalation
Follow-up
10 weeks
Study design
Preclinical methods study that describes itself as proof of concept
Funding
not stated in the source

The paper reports target engagement and tolerability, not a clinical or behavioral benefit.

Read the original source
Bench handling: soluble, stable for one month, no tight heparin binding for DNSP-11

Cell study

Kelps KA et al. Neuropeptides. 2011;45(3):213-8. PMID 21507484.

Far-UV circular dichroism showed the three GDNF-derived peptides are soluble and act independently in vitro, and reverse phase HPLC with mass spectrometry showed all three were stable for one month across a range of storage and experimental conditions. DNSP-17 bound heparin as tightly as GDNF, while DNSP-5 and DNSP-11 did not, which the authors expected to help delivery in vivo.

Participants / model
No treated organism; peptide preparations and HEK-293 cells
Treatment
Peptide solutions under stated storage and experimental conditions
Follow-up
One month of stability testing
Study design
Original preclinical bench study
Funding
not stated in the source

This is bench stability, not a shelf-life or reconstitution claim for a vendor product.

Read the original source

Why is DNSP-11 in C tier?

C fits a coherent animal record with no human exposure. The work comes from one group and covers dopaminergic effects in cells and rats and a macaque tolerability and target-engagement study, but no person has a recorded dose and the program has not reached a registered trial in the 16 years since the founding paper. The mood claim has no supporting literature at all, and the mitochondrial claim rests on one cell-line observation.