Behavioral effects of non‐opioid antitussive anticonvulsants

Abstract

Many of the currently used anticonvulsants possess a host of undesirable pharmacological properties. Several non-opioid antitussives bind to high-affinity [3H]dextromethorphan sites in brain and have novel anticonvulsant activity. Because these compounds may lack side effects possessed by currently used anticonvulsants, they may be useful in the treatment of some epilepsies, either alone or as adjuncts. Behavioral effects of these as well as clinically used anticonvulsant drugs were studied under a standard preclinical test of sedative-hypnoticianxiolytic activity which generally yields positive results with standard anticonvulsants. Lever-press responses of male Sprague-Dawley rats were maintained under a multiple schedule of food presentation in which responses in one component were suppressed by brief electric shock (punishment) whereas responses in an alternate component were not punished. The drug doses tested were the ED50 and 2 x ED50 for anticonvulsant activity against maximal electroshock-induced convulsions. The non-opioid antitussive anticonvulsants, carbetapentane, caramiphen, dextromethorphan, as well as diphenylhydantoin, did not increase punished responding. Nonpunished responding was unaffected by EDs0 dose levels of these compounds. In contrast, diazepam increased punished responding to 800% of control levels and increased nonpunished responding at 1 mgikg. Responding was typically decreased by the highest doses of all drugs studied except diphenylhydantion. Thus, the non-opioid antitussive anticonvulsants were devoid of significant behavioral effects at the EDs0 dose and did not possess the anxiolytic activity of benzodiazepine or barbiturate anticonvulsants.