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A comparative cross over study of the action of tiapride and meprobamate in behaviour problems with motor and verbal agitation was conducted on 42 hospitalized patients. Tiapride was shown to be statistically superior as far as its efficacy on agitation and its tolerance as it did not modified the patient's vigilance.
On a residential research ward, the acute effects of placebo, lorazepam (LZ) (1.5-9.0 mg) and meprobamate (MEP) (600-3600 mg) were examined using a within-subject double-blind Latin Square design in nine male subjects with histories of drug abuse. Drug effects were assessed with objective performance tasks, subject estimates of performance, staff ratings of drug effects and subject ratings of drug effects, sleep, mood, drug liking and monetary street value. Generally, both LZ and MEP produced comparable dose-related effects; LZ had a more rapid onset of action and on several measures showed a more shallow dose-response curve than MEP. With LZ, but not MEP, subjects under-estimated the degree to which their performance was impaired and under-rated drug effects as compared to analogous staff ratings. Both drugs produced sedation-like subject ratings of mood and sleep but generally did not produce tranquilization-like ratings. MEP produced subject ratings of drug liking and monetary street value which were equal to or in some cases greater than those of LZ. Relative potency estimations showed that LZ was 510 to 783 times more potent than MEP in producing performance impairment but was only 370 times more potent than MEP in producing subject ratings of drug liking. Overall, these data indicate that the likelihood of abuse of MEP is at least equal to if not greater than that of LZ although LZ may have a greater likelihood of producing adverse behavioral effects such as a performance impairment and under-estimates of the degree of impairment. These data in conjunction with previous results from this laboratory show that the behavioral effects of benzodiazepines can be differentiated from those of other types of sedative/anxiolytics and that MEP displays characteristics of a barbiturate-like profile of action.
The combination of meprobamate and diphenhydramine increased tyrosine hydroxylase activity in the rat nucleus locus coeruleus after twice daily injections, whereas neither compound alone had an effect. Increased activity occurred using a variety of medication ratios and absolute doses.
A semiautomated method has been developed for the analysis of tablets containing tridihexethyl chloride in combination with meprobamate. The method is based on the USP assay for tridihexethyl chloride in tablets. The active ingredient is dissolved in water, the aqueous solution is mixed with buffer and dye solution, and the dye complex is extracted into chloroform. The absorbance of the chloroform solution is monitored at 408 nm. Results from the semiautomated method agree with results for the USP method. Recoveries from authentic formulations show no interference from the excipients tested.
Three polymorphic meprobamate-modifications (I, II, III) of different particle size were compressed without other ingredients on a hydraulic press under 30, 60, 120, and 240 N/mm2. The rather soft substance shows a high degree of densification and above ca. 60 N/mm2 also good consolidation properties. The void volumes of the compacts obey the equation of Kawakita and are increasing in all cases in the sequence I leads to III leads to II. The radial breaking strength generally decreases in the same succession and depends linearly on the logarithm of compaction pressure. It is noteworthy, that the modification with the highest density (I) has the highest plasticity and is also compacted most easily. Modification II which is slightly harder and has a density between modifications I and III, shows the greatest differences in the compaction behaviour, as compared to modification I. Its breaking strength is also increasing faster with compaction pressure than the other modifications.
The authors draw attention to the fact that the decrease in 17-hydroxycorticosteroids and 17-ketosteroids observed in patients under meprobamate treatment is probably due to chemical interference with assay methods, since normal response to metyrapone indicates that the adrenal function is unimpaired. The asthenia usually reported by these patients is due to depression and should not be blamed on deficiency of the adrenal cortex.
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