Anticonvulsant effects of propranolol and their pharmacological modulation.
The anticonvulsant activity of propranolol was investigated in mice and rats using the electroshock seizure test (MES) and in special cases the electrically evoked hippocampal afterdischarges as a model. The results show that racemic propranolol as well as the two enantiomers were effective against MES. (+)-propranolol, the isomer with negligible beta-adrenoceptor blocking capacity revealed the stronger effect, its efficacy was comparable with the potency of phenobarbital, an overadditive synergism could be demonstrated. Subchronic administration of the two enantiomers led to a significantly reduced ED50 value of (-)-propranolol 24 h after the last application, the (-)-isomer became more effective. The (+)-propranolol did not reveal significant differences. In unrestrained rats with chronically implanted electrodes propranolol increased the stimulation threshold and reduced the duration of electrically evoked hippocampal afterdischarges. Investigations with drugs affecting monoaminergic systems in the CNS demonstrated that the noradrenergic system might play a predominant role in modulating the anticonvulsant effectiveness of propranolol. Pharmacological suppression (6-hydroxydopamine, reserpine, phenoxybenzamine) or stimulation (maprotiline, yohimbine, clenbuterol) reduced or enhanced the activity of propranolol against MES. On the other hand, manipulation of the serotonergic or dopaminergic system seemed to be less effective. In general, the findings confirm the results of previous studies that the membrane stabilizing property and not the blocking action on beta adrenergic (or serotonergic) receptors accounts for the anticonvulsant activity of propranolol.
D000818:Animals; D000927:Anticonvulsants; D004298:Dopamine / Q000502:physiology; D004347:Drug Interactions; D004569:Electroencephalography; D004597:Electroshock; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology; D013237:Stereoisomerism; D013997:Time Factors
D000927:Anticonvulsants; D012701:Serotonin; D011433:Propranolol; D004298:Dopamine; D009638:Norepinephrine