The central hypotensive action of baclofen in the anaesthetized cat

In the pentobarbital-anaesthetized cat, the intracerebroventricular administration of 20 microgram/kg d,1-baclofen led to marked hypotension and bradycardia, whereas the same dose of d-baclofen (i.c.v.) had no cardiovascular effect. When the drug was prevented from reaching the brain stem structures by collecting perfusate through a catheter lodged in the Aqueduct of Sylvius, the efficacy of d,1-baclofen was increased. Bicuculline did not antagonize the central cardiovascular effects of d,1-baclofen at doses which inhibit the cardiovascular effects of GABA agonists. However, both glutamic acid and kainic acid prevented and reversed the central hypotension and bradycardia produced by d,1-baclofen. These effects of baclofen may therefore be mediated by a selective inhibition of the release of the excitatory neurotransmitter, glutamate, within forebrain structures involved in central cardiovascular regulation.