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.
Nagatani
T
T
Department of Pharmacology, Asahi Chemical Industry, Miyazaki, Japan.
Yamamoto
T
T
Takao
K
K
Hashimoto
S
S
Kasahara
K
K
Sugihara
T
T
Ueki
S
S
D000374:Aggression / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D003220:Conflict, Psychological; D004327:Drinking Behavior / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D012701:Serotonin / Q000378:metabolism; D058924:Thienopyridines; D013874:Thiopental / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D009125:Muscle Relaxants, Central; D011725:Pyridines; D058924:Thienopyridines; D013876:Thiophenes; C066285:N-cyclohexyl-1,2,3,4-tetrahydro(1)benzothieno(2,3-c)pyridine-3-carboxamide; D012701:Serotonin; D000431:Ethanol; D005442:Flumazenil; D006897:Hydroxyindoleacetic Acid; D013874:Thiopental