Bicuculline actions on isolated rat atria, mouse vas-deferens and guinea-pig ileum are unrelated to GABA A receptor blockade.
1. Some new pharmacological activities of bicuculline were found in isolated rat atria, mouse vas deferens and guinea-pig ileum. 2. In isolated rat atria bicuculline (10-300 microM) induced potent positive inotropic and negative chronotropic effects which were not antagonized by propranolol (1 microM), 6-hydroxydopamine pretreatment (50 mg/kg i.v. twice), ranitidine (3 microM) or atropine (1 microM). Bicuculline (10-300 microM) potentiated electrically evoked contractions in mouse vas deferens and inhibited them (30-500 microM) in guinea-pig ileum. It was inactive on unstimulated mouse vas deferens. 3. The above effects were completely reproduced by the bicuculline related-substance, beta-hydrastine, but not by the bicuculline N-methyl derivative, bicuculline methiodide (BMI), on the isolated rat atria. BMI inhibited instead of potentiating the mouse vas deferens twitches and potentiated instead of inhibiting the guinea-pig ileum twitches. 4. Picrotoxin, the other classic non-competitive GABA A antagonist, was completely devoid of the effects reported for bicuculline. 5. We concluded that, on the three preparations studied, bicuculline possesses some effects which are unrelated to its GABA A receptor blocking activity.
Bartolini
A
A
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Giotti
A
A
Giuliani
S
S
Malmberg-Aiello
P
P
Patacchini
R
R
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D003292:Convulsants; D004347:Drug Interactions; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009197:Myenteric Plexus / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D003292:Convulsants; D011963:Receptors, GABA-A; D001640:Bicuculline