Propranolol and metoprolol enhance the anticonvulsant action of valproate and diazepam against maximal electroshock

• Published in: Pharmacology, biochemistry and behavior Vol. 71; no. 1; pp. 223 - 231
• Main Authors: Luchowska, Elżbieta, Luchowski, Piotr, Wielosz, Marian, Kleinrok, Zdzisław, Czuczwar, Stanisław J., Urbańska, Ewa M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.01.2002; Elsevier Science
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Animals; Anticonvulsant drugs; Anticonvulsants - metabolism; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biological and medical sciences; Catecholaminergic system; Diazepam; Diazepam - metabolism; Diazepam - therapeutic use; Drug Synergism; Drug Therapy, Combination; Electroshock; Epilepsy; Male; Maximal electroshock-induced seizures; Medical sciences; Metoprolol; Metoprolol - therapeutic use; Mice; Motor Activity - drug effects; Motor Activity - physiology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Propranolol; Propranolol - therapeutic use; Valproate; Valproic Acid - metabolism; Valproic Acid - therapeutic use; β-Adrenergic receptor antagonist; Maximal electroshock-induced seizures; Metoprolol; Epilepsy; Anticonvulsant drugs; Propranolol; β-Adrenergic receptor antagonist; Diazepam; Valproate; Nervous system diseases; Drug combination; Intraperitoneal administration; Rodentia; Anticonvulsant; Valproate semisodium; Cerebral disorder; β-Adrenergic receptor; Locomotion; Vertebrata; Mammalia; Convulsion; Mouse; Animal; Central nervous system disease; Benzodiazepine derivatives; Drug interaction; Antagonist; Neurological disorder
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(01)00654-2

The anticonvulsive potential of classical antiepileptics co-administered with β-adrenergic receptor antagonists against generalized tonic–clonic seizures was evaluated in the model of maximal electroshock (MES)-induced convulsions. Propranolol, acebutolol, metoprolol and atenolol were tested in the doses not affecting the electroconvulsive threshold. Propranolol and metoprolol lowered the ED 50 of valproate and diazepam. Acebutolol reduced valproate's but not diazepam's ED 50 value. In contrast, hydrophilic atenolol, not penetrating via blood–brain barrier, affected neither the action of valproate nor diazepam. None of the studied drugs changed the protective activity of carbamazepine and phenytoin against MES. β-blockers per se did not alter the motor performance of mice. Moreover, propranolol and metoprolol did not influence diazepam-evoked impairment of locomotor activity. The free plasma and brain levels of antiepileptic drugs were not affected by β-blockers. In conclusion, the use of certain β-adrenoceptor antagonists, such as propranolol and metoprolol, might improve the antiepileptic potential of valproate and diazepam.