ABSTRACT
Biologic Effects of Barbiturates in Mammals • PB and Other Barbiturates as Mammalian Tumor Promoters • Induction of Specific Proteins in Mammals by Barbiturates • Species and Strain Differences in Response to Barbiturates and Barbiturate Analogs Induction of Specific Proteins by Barbiturates in Nonmammalian Organisms • Induction by Barbiturates of P450 Cytochromes in B acillus m egaterium Barbiturate-Mediated Induction of Specific Proteins in Rodents • Induction of Rat a -1-Acid Glycoprotein (Orosomucoid) by PB • Induction of Rat CYP2B1 and CYP2B2 (Cytochromes P450b/P450e) by
Phenobarbital • Apparent Conflicts Among Various Laboratories Regarding the Mechanism of
Induction of the Rat CYP2B1/2 Genes by Phenobarbital Conclusions and Future Perspectives Acknowledgment References
BIOLOGIC EFFECTS OF BARBITURATES IN MAMMALS
Phenobarbital (PB) and many other barbiturates have a variety of biologic effects in mammals, some of which apparently are unrelated. The sedative and anticonvulsant effects of barbiturates are well known, and barbiturates (especially PB) have been used medically to relieve insomnia and to prevent seizures, particularly in epilep tics. Other medical uses of specific barbiturates include the treatment of a variety of anxiety-tension states and, for exceptionally short-acting derivatives, utilization as general anesthetics. Mechanistically, barbiturates can be classified as lipophilic gamma aminobutyric acid (GABA)—receptor agonists that function to inhibit the ex citable cells of the central nervous system and other tissues. Most of the neurologic effects of barbiturates can be attributed, in part at least, to their interaction with GABA receptors or, in some cases, to their physical interaction with and modification
of biologic membrane lipids (1). Other biologic alterations mediated by barbiturates, however, cannot be explained easily by GABA-receptor or membrane-interaction mechanisms. These include tumor promotion, especially in the liver in some mam malian species, and the induced expression of specific P450 cytochromes and a num ber of other proteins in humans and other higher animals.
