Inhibitory effect of benzodiazepines on the reflex swallowing.

Abstract

Benzodiazepines and other central nervous system depressants may affect central structures for swallowing. However, no knowledge is available about their site and mode of action. Vagotomized, artificiallyrespirated rabbits awaked from anesthesia as well as decerebrate dogs or those with encéphale isole were employed. Electromyographic activities of swallowing-relevant muscles(mylohyoideus and inferior constrictor) and intrapharyngeal pressure were recorded. Thus, the duration of pharyngeal phase of swallowing(SWD) and the degluticatory pharyngeal pressure(SWP) were measured. All drugs were intravenously administered in most experiments. 1) Fludiazepam, diazepam (DZP), nitrazepam and oxazolam exerted an inhibitory effect on swallowing in unanesthetized animals. Thus, both SWP and SWT) were markedly reduced, while the temporal sequence of muscle activities during swallowing were left unaffected. A dose-response study in the SWD effect yielded their ED50 values: 0.002, 0.02, 0.13 and 1.08mg/kg, respectively. Thiamylal(0.25mg/kg), thiopental(TPL, 0.5mg/kg), pentobarbital(2mg/kg), phénobarbital(4mg/kg), urethane(20mg/kg), ketamine(lmg/kg) and lidocaine(2mg/kg) had almost the same effect on swallowing. 2) The effect of DZPcould be reversed by a convulsive dose of Picrotoxin or bicuculline and by dimorpholamine. Among them, Picrotoxin alone could prevent it. 3) Decortication or midbrain transection markedly reduced or almost abolished the inhibitory effects of DZP and TPL. Both drugs also suppressed the degluticatory activities when injected into a vertebral artery. They appear to cause a selective blockade of degluticatory control from higher centers, which are subject to the ascending reticular activation. Potentiation of GABA-mediated pre- and postsynaptic inhibitions might probably contribute to the degluticatory effect of benzodiazepines. In fact, DZP disturbed water-swallowing of conscious dog to coughing.