Nasycrine

Nasycrine is a synthetic heterocyclic compound belonging to the class of substituted triazolo[4,5-b]pyridines. Its molecular formula is C13H11N5 and it possesses a triazole ring fused to a pyridine core, with a para‑methyl substituent and a 2‑chloro substitution on the aromatic system. The compound is obtained through a multistep synthesis beginning with 4‑chloro‑2‑aminopyridine, which undergoes diazotization and subsequent cyclization with sodium azide to form the triazole moiety. Final methylation is achieved by treatment with methyl iodide in the presence of a base such as potassium carbonate.

In vitro studies demonstrate that nasycrine acts as a high‑affinity antagonist at the human serotonin 5‑HT2A receptor, with an IC50 of approximately 45 nM. It also shows moderate affinity for dopamine D2 receptors (IC50 ~ 120 nM) and negligible activity at muscarinic or adrenergic receptors. Pharmacokinetic profiling in rodent models indicates oral bioavailability of about 60%, a half‑life of roughly 4.5 hours, and predominant hepatic metabolism via CYP3A4 oxidation.

Preclinical animal studies report anxiolytic and antidepressant‑like effects, attributed to 5‑HT2A receptor blockade. Clinical trials are currently limited to Phase I, assessing safety, tolerability, and dose‑range in healthy volunteers. No serious adverse events have been reported, though mild nausea and headache are noted at higher doses. No specific drug interactions have been identified, but caution is advised in patients with hepatic impairment.

Regulatory agencies have granted investigational new drug status for nasycrine in several jurisdictions. Further research is underway to clarify its therapeutic potential for treatment‑resistant depression and other serotonergic disorders.