GTS-21 (DMBX-A): A Comprehensive Pharmacological and Clinical Development Review of a Selective α7 Nicotinic Agonist

Executive Summary

GTS-21, also known as DMBX-A, is an investigational small molecule that emerged from a focused effort to therapeutically target the neuronal α7 nicotinic acetylcholine receptor (α7 nAChR). Derived from the natural marine toxin anabaseine, GTS-21 was designed as an orally active, selective partial agonist for this receptor, which plays a critical role in both central nervous system (CNS) cognitive functions and the peripheral cholinergic anti-inflammatory pathway. The scientific rationale for its development was compelling, offering the potential for a dual-mechanism therapy to address the cognitive deficits and neuroinflammation implicated in conditions such as Alzheimer's disease (AD) and schizophrenia.

Preclinical studies painted a promising picture, with GTS-21 demonstrating cognitive enhancement in various animal models, neuroprotective effects against amyloid-beta toxicity, and potent anti-inflammatory activity in models of sepsis and arthritis. This promise was further bolstered by an early-phase human trial in healthy volunteers, which reported not only an excellent safety and tolerability profile but also statistically significant improvements in attention and memory. These findings provided a strong impetus for advancing GTS-21 into patient populations.