New benzamide-derived 5-HT3 receptor antagonists which prevent the effects of ethanol on extracellular dopamine, and fail to reduce voluntary alcohol intake in rats.
A set of substituted benzamides, characterized by the presence of a bulky quinolizidine moiety, were subjected to binding assays for 5-HT3 and D2 receptors on membranes obtained from the bovine area postrema ([3H]-GR65630) and the rat striatum ([3H]-spiperone) respectively. These benzamides resulted unsuitable for the recognition of D2 receptors, while a few of them, devoid of 5-HT4 receptor activity, had consistent affinity for central 5-HT3 receptors, inhibiting also potently the ethanol-induced dopamine efflux from the mesolimbic dopamine terminal region. However they failed in attenuating voluntary alcohol consumption in rats, as observed with several other chemically unrelated 5-HT3 antagonists. Thus the 5-HT3-mediated inhibition of alcohol-induced striatal release of dopamine by substituted benzamides is not a requisite for affecting ethanol intake.
Iusco
G
G
Istituto di Scienze Farmaceutiche, Università di Genova, Italy.
Boido
V
V
Sparatore
F
F
Colombo
G
G
Saba
P L
PL
Rossetti
Z
Z
Vaccari
A
A
D000428:Alcohol Drinking; D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D001549:Benzamides; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D000431:Ethanol; D004298:Dopamine