GTS‑21
Alpha-7 nicotinic partial agonist (DMXB-A) with phase 2 human trials and moderate evidence.
Pharmacology
Contents
WHAT IS GTS-21?
Detailed overview
GTS-21 (DMXB-A, 3-(2,4-dimethoxybenzylidene)anabaseine) is a synthetic derivative of the marine toxin anabaseine and a partial agonist of the alpha-7 nicotinic acetylcholine receptor (α7 nAChR). The α7 receptor is an important regulator of attention, working memory and sensory gating, so GTS-21 was developed primarily to improve the cognitive deficit and impaired sensory gating associated with schizophrenia. In humans it reached phase 1 and phase 2 trials, tested in both healthy volunteers and patients with schizophrenia, but cognitive efficacy was inconsistent across studies, partly due to its short half-life and the fluctuating plasma levels of its active metabolite. It has also shown anti-inflammatory and neuroprotective effects in preclinical models via the cholinergic anti-inflammatory pathway.
Mechanism
α7 nAChR partial agonist
Evidence
Phase 2 human trials (not approved)
Legal status
Experimental, unapproved drug
Receptor profile
- Alpha-7 nicotinic acetylcholine receptor (α7 nAChR)Strong
- Glutamatergic / dopaminergic signaling (indirect)Moderate
- Cholinergic anti-inflammatory pathway (NF-κB suppression)Moderate
- Alpha-4-beta-2 nicotinic receptor (weak antagonism)Weak
Safety
Side effects, stop signs, contraindications
Side effects · 5
- Gastrointestinal complaints: nausea, abdominal discomfort, occasional vomiting at higher doses
- Headache and dizziness reported in human trials
- Short half-life and an active metabolite (4-OH-GTS-21) cause fluctuating plasma levels and effect
- Efficacy was inconsistent across phase 2 trials: cognitive benefit was not always confirmed
- Long-term safety in humans is unclear; there is no approved therapeutic use
Contraindications · 4
- Pregnancy and breastfeeding: safety not established, avoid
- Unapproved experimental compound; not recommended without clinical supervision
- Active gastrointestinal disease: nausea and GI effects may aggravate it
- Unknown interaction profile: caution with cholinergic and psychoactive agents
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers
Kitagawa H, Takenouchi T, Azuma R, et al.
Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia
Olincy A, Harris JG, Johnson LL, et al.
Initial phase 2 trial of a nicotinic agonist in schizophrenia
Freedman R, Olincy A, Buchanan RW, et al.
Effects of an alpha 7-nicotinic agonist on default network activity in schizophrenia
Tregellas JR, Tanabe J, Rojas DC, et al.
Pharmacokinetic Limitations on Effects of an Alpha7-Nicotinic Receptor Agonist in Schizophrenia
Kem WR, Olincy A, Johnson L, et al.
FAQ
FAQ
Alpha-7 nicotinic partial agonist (DMXB-A) with phase 2 human trials and moderate evidence.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.