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.