Peptide Schedule
DNSP-1111 residuesPPEAPAEDRSLEach bubble = one amino acid. Size = residue mass. Color = chemical class.DNSP-11
Benefits
About DNSP-11
DNSP-11 (Dopamine Neuron Stimulating Peptide-11) is a synthetic 11-amino-acid peptide derived from the proprotein region of human glial cell line-derived neurotrophic factor (GDNF). It was identified through a post-translational processing model which predicted that the GDNF prosequence could be cleaved at internal dibasic endopeptidase sites to yield smaller, amidated bioactive peptides. In cell culture, DNSP-11 supports the survival of fetal mesencephalic dopaminergic neurons, increasing both cell number and neurite outgrowth. It blocks staurosporine- and gramicidin-induced cytotoxicity in dopaminergic B65 cells by preventing cytochrome c release from mitochondria. Importantly, its neuroprotective activity does not appear to depend on binding the canonical GFR-alpha-1 receptor used by full-length GDNF, suggesting a distinct signaling pathway involving ERK1/2 phosphorylation. In vivo, a single injection of DNSP-11 into the rat substantia nigra increased resting dopamine and DOPAC levels by approximately 100% with effects persisting up to 28 days. In 6-OHDA lesioned rats (a standard Parkinson's disease model), it reduced apomorphine-induced rotational behavior by roughly 50%. Intranasal administration studies in rats showed that 125-I-labeled DNSP-11 distributed throughout the brain within 30 minutes, reaching the striatum and substantia nigra. Repeated intranasal dosing at 300 mcg in rats increased dopamine turnover in both the striatum and substantia nigra. Non-human primate studies confirmed tolerability of repeated intranasal delivery at escalating doses up to 10 mg/day over 10 weeks without adverse behavioral effects or weight loss. All existing evidence comes from rodent and non-human primate studies. No human clinical trials have been initiated. The long-term safety profile in humans is completely unknown, and this compound should be considered strictly experimental.
Who Should Consider DNSP-11
- Researchers investigating GDNF-pathway neurotrophic factors for dopaminergic neuroprotection
- Scientists studying preclinical approaches to Parkinson's disease
- Individuals exploring experimental neuroprotective peptides under medical supervision
- Those researching intranasal delivery of neurotrophic factors to the central nervous system
How DNSP-11 Works
DNSP-11 is derived from the proprotein domain of GDNF and acts as a neurotrophic factor for dopaminergic neurons through a pathway that does not require the canonical GFR-alpha-1/RET receptor complex used by mature GDNF. Instead, DNSP-11 activates ERK1/2 (extracellular signal-regulated kinase) phosphorylation, a key signaling cascade involved in neuronal survival, differentiation, and synaptic plasticity. This activation promotes cell survival by preventing mitochondrial cytochrome c release, thereby blocking the intrinsic apoptotic pathway. In dopaminergic neurons, DNSP-11 increases dopamine synthesis and turnover, as demonstrated by elevated DOPAC/dopamine ratios in treated animals. The peptide is rapidly taken up into neurons following direct injection and maintains its biological effects for extended periods (up to 28 days from a single intranigral injection in rats), suggesting it may trigger sustained intracellular signaling cascades or gene expression changes rather than acting solely through acute receptor activation.
What to Expect
No established human timeline exists. In animal models, neurochemical changes (increased dopamine turnover) were measurable within the first week of repeated intranasal dosing. Any perceived effects in humans during this window are speculative.
In rat studies, 3 weeks of repeated intranasal dosing at 300 mcg produced measurable increases in dopamine turnover in both the striatum and substantia nigra. Neuroprotective effects in 6-OHDA lesion models were apparent in this timeframe.
Extended dosing data comes from non-human primate studies where 10 weeks of repeated intranasal delivery was well tolerated. In rats, a single intranigral injection maintained elevated dopamine levels for up to 28 days, suggesting prolonged duration of activity.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 100mcg | Daily |
| Moderate | 300mcg | Daily |
| Aggressive | 500mcg | Daily |
Note: GDNF propeptide-derived 11-amino-acid neuroprotective peptide. Intranasal or subcutaneous. Preclinical only — no human trials have been conducted. All dosing is extrapolated from rat and non-human primate studies.
How to Inject DNSP-11
Intranasal: reconstitute and deliver via nasal spray, alternating nostrils. The intranasal route provides direct CNS access via olfactory and trigeminal nerve pathways and is the best-studied delivery method for this peptide. In animal studies, total intranasal volume was 50 mcL divided across both nostrils in small droplets. Subcutaneous: inject into abdominal fat once daily, rotating injection sites. Start at the lowest dose and titrate gradually. This is a preclinical research compound with no established human dosing — all doses are extrapolated from animal studies.
Cycling Protocol
No established human cycling protocols exist. The 4-on/4-off recommendation is precautionary given the complete absence of long-term human data. In rat studies, 3-week repeated intranasal dosing was used. In non-human primates, 10-week repeated dosing was tolerated. Discontinue immediately if any adverse effects occur.
Pharmacokinetics
Source: No formal pharmacokinetic half-life data published for DNSP-11. A single intranigral injection maintained elevated dopamine and DOPAC levels for up to 28 days in rats, suggesting prolonged biological activity far exceeding the expected plasma half-life of an 11-amino-acid peptide. Intranasal tracer studies showed brain distribution within 30 minutes.
Loading the interactive decay curve.
Side Effects
No human safety data exists. All information comes from animal studies. In rat studies, no observable adverse effects were reported at the doses tested. In non-human primate dose-escalation studies (up to 10 mg/day intranasally for 10 weeks), no adverse behavioral effects or weight loss were observed. Potential side effects in humans are entirely unknown. Full-length GDNF protein has been associated with anti-GDNF antibodies in clinical trials, but whether DNSP-11 carries similar immunogenic risk is unstudied.
Contraindications
- Pregnancy or breastfeeding — no reproductive toxicology data exists for this compound
- Individuals under 25 — effects on developing nervous systems are entirely unstudied
- Active cancer or history of CNS tumors — neurotrophic stimulation could theoretically promote tumor growth
- Known hypersensitivity to GDNF-derived compounds
- Individuals taking dopaminergic medications (levodopa, dopamine agonists) — combined effects on dopamine levels are unstudied and could be unpredictable
Drug Interactions
- Levodopa/carbidopa — DNSP-11 increases endogenous dopamine levels; combined use could theoretically lead to dopaminergic excess
- Dopamine agonists (pramipexole, ropinirole) — additive dopaminergic effects are unstudied and may carry risk
- MAO-B inhibitors (selegiline, rasagiline) — both increase dopamine availability through different mechanisms; interaction effects unknown
- Antipsychotics (dopamine antagonists) — may counteract the dopaminergic effects of DNSP-11; no interaction data exists
- Other neurotrophic peptides (Cerebrolysin, Semax, P21) — no combination data available; use caution when stacking
Storage & Stability
Molecular Profile
Related Peptides
References
- Dopamine neuron stimulating actions of a GDNF propeptide (Bradley et al., 2010)PubMed 20305789
- Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro (Kelps et al., 2014)PubMed 24406899
- Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson's disease (Stenslik et al., 2015)PubMed 25999268
- Methodology and effects of repeated intranasal delivery of DNSP-11 in awake Rhesus macaques (Stenslik et al., 2018)PubMed 29614295
- Evaluation of the physical and in vitro protective activity of three synthetic peptides derived from the pro- and mature GDNF sequence (Bradley et al., 2011)PubMed 21507484