Benzylamine-related compounds stimulate rat vas deferens neurotransmissionand potentiate memory in the mouse acting as potassium channel blockers

In stimulated rat vas deferens, the new compound 2,6-dibutylbenzylamine (B2 5) and some related benzylamines, first potentiated then completely inhibit ed electrically-induced twitch response, showing the biphasic effect previo usly observed in unstimulated preparations. To verify if this effect could be referred to as a modulation of potassium channels the activity of some b enzylamines, KCl, tetraetylammonium (TEA), BaCl2, 4-aminopyridine (4-AP), g libenclamide (GLI), charibdotoxin (ChTX) and apamin (APA) has been compared . While KCI and benzylamine-related derivatives induced biphasic effects, T EA, 4-AP, BaCl2, GLI stimulated but were unable to inhibit the twitches. Th e pretreatment with stimulating concentrations of TEA, 4-AP, GLI, APA or Ch TX and B25, as reference compound in the benzylamine series, dose-dependent ly reduced the stimulatory effect of KCl but were unable to modify the inhi bitory effect induced by this ion. Both KCl and B25 potentiated each others own inhibitory effect suggesting that, unlike other potassium channel bloc kers, they could modulate in an opposite way voltage-dependent potassium ch annels in order to facilitate and then depress neurotransmission. In other experiments, benzylamines, KCl, TEA, 4-AP and GLI reverted the inhibitory e ffect of cromakalim and omega-conotoxin GVIA (omega-CTX). This effect furth er supports a common mechanism of action (potassium channel blockade) proba bly inducing the opening of Ca2+ channels different from N or L in the prep aration. Finally, the prevention of minoxidil-induced amnesia in the mouse by B25 and related benzylamines, comparable to the same effect shown by TEA and 4-AP, indicates that these compounds are endowed with potential pharma cological activity in the CNS as well. (C) 2000 Academic Press.