Pharmacological profile of a potential anxiolytic: AP159, a new benzothieno-pyridine derivative

AP159 [N-cyclohexyl-1,2,3,4-tetrahydrobenzo(b)thieno(2,3c)pyridine]-3- carboamide,hydrochloride) showed clear anti-conflict activity in rats in the absence of effects on muscle relaxation, potentiation of anesthesia (in mice) or anticonvulsant activity (in mice). This anti-conflict effect was antagonized by treatment with Ro15-1788. By contrast with the deficits produced by diazepam, AP159 did not impair passive avoidance. The latter drug also improved scopolamine-induced amnesia in the same task. AP159 did not inhibit 3H-flunitrazepam binding, but potently inhibited 3H-8OH-DPAT binding. This compound increased serotonin and 5HIAA content of the midbrain raphe nuclei and of the amygdala centralis. AP159 has been shown to be a novel non-BZP anxiolytic agent with no side effects in laboratory animals; it could be a clinically effective anxiolytic agent.