Adverse effects on rat cardiac function ex vivo after repeated administration of the benzodiazepine partial inverse agonist, FG7142.
1. The Langendorff preparation was used to investigate functional changes in rat heart one week after the last of a course of repeated injections of the benzodiazepine inverse agonist, FG7142 (20 mg kg-1 i.p; three times weekly for five weeks). 2. Under these conditions, FG7142 caused a statistically significant reduction in both cardiac basal tension and the inotropic effect of noradrenaline at doses giving 50 and 100% of the maximum response. 3. Basal heart rate, basal coronary perfusion pressure and the effects of noradrenaline ex vivo on these parameters were all unaffected by repeated administration of FG7142. 4. FG7142 had no intrinsic effects on cardiac function when administered in vitro. 5. We discuss mechanisms which could underlie the effects of FG7142 on cardiac tension ex vivo and consider the possibility that this action may be related to the anxiogenic or proconvulsant actions of this drug.
Stanford
S C
SC
Department of Pharmacology, University College & Middlesex School of Medicine, London.
Gettins
D
D
Little
H J
HJ
D000818:Animals; D002243:Carbolines / Q000633:toxicity*; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D002243:Carbolines; D011963:Receptors, GABA-A; C035874:FG 7142; D009638:Norepinephrine