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

Abstract

ABSTRACT-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 ac tivities 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.

A novel compound JPM8: in vivo penile activity promotion in rats, effect on the relaxation and cGMP/cAMP accumulation in isolated rabbit corpora cavernosa

“…19 This process in normally proceeded by a self-grooming behavior, yawning, followed by penile erection which is physically clear, and then leading to the ultimate and final action of selfsucking which represents the end of the sexual cycle. 19,20 This is the very first report giving direct in vivo effect of PDE5 inhibitors on the improvement of erectile response in rats as an evidence of suitability for erectile dysfunction treatment. As shown in Figure 3A, increasing oral dose of JPM8 gave a very significant increase in the percentage of animals experiencing increase in their penile activity.…”

“…17 Maeda et al, while working on a series of evaluations for a cognitive enhancer using rat models, discovered a cognitive enhancer that also possesses stimulating activity on penile erection. 20 The major PDE in rabbit corpora cavernosa is PDE5, in addition to small amounts of PDE1 and PDE2. PDE3, which contributes significantly to the total PDE activity in human cavernosa, is apparently lacking in the rabbit cavernosa.…”

Inhibition of penile erection in rats by a long‐acting somatostatin analogue, octreotide (SMS 201–995)

“…A study carried to evaluate a novel cognitive enhancer, FR 121196, used the enhancement of penile erection as a sign of cholinergic activation [ 27]. The erection‐stimulating effect of FR 121196 was abolished in rats treated with a somatostatin depletor, or by lesioning the seratonergic raphe nuclei [ 33]. Thus, a classic whole‐animal study proved effective in obtaining a common somatostatinergic effect and provided some insight into the common somatostatinergic and seratonergic mechanisms underlying penile erection.…”

Aqueous root extract of Psidium guajava exhibits dependent effects on aphrodisiac indices, reproductive hormones and spermatogenesis of male Wistar rats

“…Using animal models for the initial screening to determine the aphrodisiac potential of a test drug is an accepted model. The employed model used in this research study is simple and quick [31], and can also be said to be used to evaluate the aphrodisiac and stimulating activity on penile erection against erectile dysfunction [32]. Sexual behavioural parameters such as mount and intromission frequencies are indices of sexual vigour, libido and potency [33,34].…”