Hexobarbital sleeping time, related

Comparative studies with a series of twelve C/Si pairs of the meprobamate/sila-meprobamate type (68a/68b) also revealed, with only a few exceptions, great similarities in the biological properties of the respective C/Si analogues138 (for structurally related silicon compounds see also Reference 142). The C/Si pairs were tested for their acute toxicity, and for sublethal activity the rotating rod test and the extension of hexobarbital sleeping time were used (mice, intraperitoneal administration). In addition, the metabolism of sila-meprobamate (68b) and some of its derivatives was studied139 (for this subject see Section IV). 

The duration of action and the biological half-life of many drugs are considerably shorter in male rats than in female rats. These differences are inversely related to the activity of microsomal enzymes and are under the control of sex hormones. For example, female rats have relatively prolonged hexobarbital sleeping times and low microsomal enzyme activity whereas males have short sleeping times and relatively high enzyme activity (Table 11). Administration of testosterone to... 

Many differences in overall toxicity between males and females of various species are known (Table 9.1). Although it is not always known whether metabolism is the only or even the most important factor, such differences may be due to gender-related differences in metabolism. Hexobarbital is metabolized faster by male rats thus female rats have longer sleeping times. Parathion is activated to the cholinesterase inhibitor paraoxon more rapidly in female than in male rats, and thus is more toxic to females. Presumably many of the gender-related differences, as with the developmental differences, are related to quantitative or qualitative differences in the isozymes of the xenobiotic-metabolizing enzymes that exist in multiple forms, but this aspect has not been investigated extensively. 

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