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.