The Interaction between Physostigmine and Hexobarbital in Male Rats

Abstract

Abstract The sensitivity to hexobarbital was tested with an EEG‐threshold. Hexobarbital was infused continuously in a tail vein of male rats and the dose needed to obtain a burst suppression of 1 sec. or more in the EEG (the “silent second”) was determined. In the first part of the experiments the dose response and time response of the effect of physostigmine on the hexobarbital threshold was determined. The rats were pretreated with methylatropine 2.0 mg/kg subcutaneously. Testing of three different doses of physostigmine (0.5, 1.0 and 2.0 mg/kg intraperitoneally) showed that only the highest dose raised the hexobarbital threshold. The optimal time interval between the dose of physostigmine and hexobarbital threshold to obtain this effect was found to be around 1.5 hours. In the second part of the experiment the antagonistic effect of atropine was investigated. Methylatropine (2 mg/kg intraperitoneally) combined with physostigmine (2.0 mg/kg intraperitoneally) increased the hexobarbital threshold to 117 ± 4 per cent of a pre‐experimental value. Substitution of methylatropine with atropine (8 mg/kg intraperitoneally) gave a threshold value of 94 ± 4 per cent. Atropine combined with saline gave a threshold of 85 ± 2 per cent. The corresponding value after methylatropine was 100 ± 5 per cent. Thus pretreatment with atropine can reduce the increase in dose of hexobarbital caused by the CNS‐ effects of physostigmine.