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Physical dependence on meprobamate after repeated oral administration in rats
Abstract:
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 X 2/day), PHB (100 X 2) or COD (50 X 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 MPB 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 withdrawal 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.
Insights
Meprobamate (MPB) causes physical dependence in rats, similar to phenobarbital (PHB) but unlike codeine (COD). This study confirms MPB
Area of Science:
- Pharmacology
- Neuroscience
- Toxicology
Background:
- Meprobamate (MPB) is a sedative-hypnotic drug with an established history of abuse.
- Understanding the physical dependence potential of MPB is crucial for clinical and regulatory purposes.
- Comparative studies are needed to elucidate the specific dependence liability of MPB.
Purpose of the Study:
- To compare the physical dependence potential of meprobamate (MPB) with phenobarbital (PHB) and codeine (COD) in a rat model.
- To determine if MPB induces definite physical dependence following repeated oral administration.
- To characterize the withdrawal signs and physiological changes associated with MPB, PHB, and COD in rats.
Main Methods:
- Rats were administered MPB, PHB, or COD orally twice daily for 21 days, with a 3-day withdrawal period.
- Behavioral observations and physiological parameters (weight, rectal temperature) were monitored during intoxication and withdrawal.
- Withdrawal signs were assessed to compare the physical dependence profiles of the three drugs.
Main Results:
- MPB-treated rats exhibited withdrawal behaviors and signs similar to PHB-treated rats, but distinct from COD-treated rats.
- All drug-treated groups showed weight loss post-withdrawal, with MPB and PHB groups showing delayed recovery compared to COD.
- MPB and PHB groups displayed a prolonged increase in rectal temperature after withdrawal, whereas COD induced a decrease.
Conclusions:
- Definite physical dependence, comparable to phenobarbital (PHB) but not codeine (COD), was developed in rats after repeated oral meprobamate (MPB) administration.
- The findings suggest that MPB shares a similar dependence liability profile with other established sedative-hypnotics.
- This study provides evidence for the physical dependence potential of meprobamate in a preclinical model.