A Screening Concept Based on a Hypothesis Led to the Development of a Putative Cognitive Enhancer That Stimulates Penile Erection

The Japanese Journal of Pharmacology

Isamu Yamaguchi¹  Mayako Yamazaki¹  Yoshitaka Ohkubo¹  Nobuya Matsuoka¹  Noriaki Maeda¹  Hiroyuki Arakawa¹ 

[1] Basic Research Group, Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.

关键词: FR121196;    Memory;    Penile erection;    Hippocampus;    Somatostatin;   

DOI  :  10.1254/jjp.64.147

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(33)Cited-By(3)Starting from the hypothesis that drugs which specifically activate the hippocampal cholinergic nerve activity may ameliorate memory impairments, we carried out a series of evaluations for a novel cognitive enhancer using enhancement of penile erection as a sign of cholinergic activation, and found FR64822. The compound facilitated penile erection in naive rats, and it ameliorated scopolamine-induced amnesia of rats in passive avoidance tasks with bell-shaped dose-response curves, while it dose-dependently reduced body weight gain in Zucker fatty rats. Pretreatment with sulpiride (32 mg/kg, p.o.) hardly affected the former two activities, but significantly reduced the anorectic activity in Zucker rats. Further evaluation of FR64822 derivatives characterized a second compound, FR121196, which induces penile erection and memory enhancement, but not body weight reduction. Memory enhancing and erection stimulating activities of FR121196 were abolished in rats treated with either cysteamine (200 mg/kg, s.c.), a somatostatin depletor, or lesioning of the serotonergic raphe nuclei. Thus, classic whole animal studies based on a hypothesis proved to be efficient for reaching our objective, the discovery of a new drug. They also gave us insight into the common somatostatinergic and serotonergic mechanisms underlying penile erection and memory improvement.

【 授权许可】

Unknown