CGP 35348, a new GABAB antagonist, prevents antinociception and muscle-relaxant effect induced by baclofen.
1. CGP 35348, a new GABAB antagonist, was examined on antinociception induced by (+/-)-baclofen by use of the hot plate and writhing tests in mice and the paw pressure test in rats. CGP 35348 was also studied in mice on (+/-)-baclofen-induced impairment of rota-rod performance. 2. CGP 35348, injected either i.p. (60-100 mg kg-1 in mouse) or intracerebroventricularly (i.c.v.) (0.5-2.5 micrograms per mouse; 25 micrograms per rat) prevented (+/-)-baclofen-induced antinociception. 3. CGP 35348 did not modify oxotremorine- and morphine-induced antinociception in mice and rats. 4. CGP 35348 (2.5 micrograms i.c.v. per mouse) also prevented (+/-)-baclofen-induced impairment of the rota-rod test. 5. Two other GABAB antagonists, phaclofen (50 micrograms i.c.v. per mouse) and 2-OH-saclofen (2.5 micrograms-10 micrograms i.c.v. per mouse) did not modify (+/-)-baclofen-induced antinociception. 7. These results suggest that, at present, CGP 35348 is the only compound able to antagonize (+/-)-baclofen-induced antinociception.
Malcangio
M
M
Department of Preclinical and Clinical Pharmacology, University of Florence, Firenze, Italy.
Ghelardini
C
C
Giotti
A
A
Malmberg-Aiello
P
P
Bartolini
A
A
D000700:Analgesics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010095:Oxotremorine / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects
D000700:Analgesics; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; C052329:phaclofen; D010095:Oxotremorine; D009020:Morphine; C066430:CGP 35348; D001418:Baclofen; C057491:2-hydroxysaclofen