PHYSICAL DEPENDENCE ON MEPROBAMATE AFTER REPEATED ORAL ADMINISTRATION IN RATS

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The physical dependence potential of meprobamate (MPB) was compared with that of phenobarbital (PHB) and codeine (COD) to ascertain whether MPB produces definite physical dependence in the rat. Rats were treated orally with MPB (maintenance dosage=800 mg/kg×2/day), PHB (100×2) or COD (50×2) twice a day (10:00 a.m. and 5:00 p.m.) for a total of 21 days; the treatment was ceased for 3 days after administration for 7 days, and the last dosing was performed on day 27. During intoxication and after the withdrawal, the M PB treated rats exhibited behaviour and withdrawal signs similar to those seen in the PHB treated rats, but not the COD treated rats. After withdrawal of drugs, definite weight loss was observed in all the rats given drugs, and the recovery of the MPB and PHB treated rats was clearly later than that of the COD treated rats. A long-lasting increase in rectal temperature was observed after the with-drawal in the MPB and PHB treated rats; a decrease was seen in the COD treated rats. From these results, it is concluded that definite physical dependence on MPB, similar to that on PHB but different from that on COD, was developed after repeated oral administration for a total of 21 days in the rat.
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