Central cardiovascular action of penicillin in anaesthetized dogs and rats

Penicillin (2-3 mg X kg-1) administered into the cisterna magna (i.c.) of dogs anaesthetized with alpha-chloralose induced a significant increase in mean blood pressure (MBP) and bradycardia, whereas intravenous injections of the same doses had negligible effects. Moreover, dogs receiving central injections of penicillin showed seizures abolished by administration of decamethonium bromide (100 micrograms X kg-1, i.v.). In urethane anaesthetized rats, intracerebroventricular (i.c.v.) injections of penicillin (0.3-3 mg X kg-1) caused dose-dependent increases in mean blood pressure while the intravenous route led to opposite effects. gamma-aminobutyric acid (GABA) (1 mg X kg-1), its agonist muscimol (2 micrograms X kg-1) and the alpha 2-adrenoceptor agonist clonidine (1 micrograms X kg-1) injected intracisternally induced hypotension and bradycardia in dogs. These effects were abolished in animals pretreated with penicillin. In rats, the same agents injected intraventricularly respectively at 0.5 mg X kg-1, 0.5 micrograms X kg-1 induced also hypotension. The effect of clonidine only, was antagonized by pretreatment with penicillin, while penicillin administered at the peak of the hypotensive effect caused by GABA or muscimol reversed it. It is suggested that penicillin acts centrally as a GABA-antagonist, and that the cardiovascular effects of clonidine seem to be mediated, at least in part, by the stimulation of a GABAergic pathway controlling the autonomic nervous system.