Cyclosporin Increases the CNS Sensitivity to the Hypnotic Effect of Phenobarbitone but not Ethanol in Rats

Abstract— The purpose of this investigation was to determine whether repetitive administration of cyclosporin affects the pharmacodynamics of phenobarbitone‐ and ethanol‐induced anaesthesia. Sabra male rats received either cyclosporin (50 mg kg⁻¹ day⁻¹, i.m.) for four days, or the same volume of the vehicle. Two hours after the last cyclosporin dose, phenobarbitone or ethanol solutions were infused intravenously at a constant rate until the onset of anaesthesia. Repetitive treatment with cyclosporin increased the CNS sensitivity to the hypnotic action of phenobarbitone. This was evidenced by the lower CSF phenobarbitone concentration, at the onset of the hypnotic effect, in the cyclosporin‐treated group vs control values (115 ± 4 vs 93 ± 7 mg L⁻¹, P = 0·01). However, the same pretreatment had no apparent effect on the pharmacodynamics of ethanol‐induced sleep. It is suggested that anaesthesiologists must be alert to the possible increase in brain sensitivity when placing cyclosporin patients under anaesthesia with barbiturates. 1994 Royal Pharmaceutical Society of Great Britain