Investigation of clonidine and lofexidine for the treatment of barbiturate withdrawal in mice

Abstract

This study was designed to determine the effectiveness of clonidine (CL) and CL analogue, lofexidine (LF), in reducing the incidence and/or severity of convulsion associated with barbiturate withdrawal in mice. CL and LF have been shown to be useful in blocking opioid withdrawal symptoms in rodents and man. Some of the symptoms and possibly the mechanism(s) of the barbiturate withdrawal syndrome are similar to those of the opioid withdrawal syndrome. Therefore, we hypothesized that LF and CL may be efficacious in treating barbiturate withdrawal. The method of Belknap et al as modified by Blum et al for inducing barbiturate dependence in mice was used. Phenobarbital was thoroughly mixed with the animals' milled diet. After 10 days 45 pre-treated mice were divided into withdrawal, control, clonidine- and lofexidine-treated groups. Withdrawal scores were graded as 0 = no effect, 1 = tremor, 2 = wild running, 3 = tonic-clonic seizures, 4 = death, and were collected for each group every 5 hr for 2.5 days. The data in this model suggest that CL and LF offer no protective effect in treating barbiturate withdrawal-induced seizures in mice.