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Copyright © 2000 by Institute of Pharmacology Polish Academy of Sciences |
Pol. J. Pharmacol., 2000, 52, 359-365 ISSN 1230-6002 |
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Effects of some centrally active drugs on the allopregnanolone synthesis in rat brain.
L. JAWORSKA-FEIL, B. BUDZISZEWSKA, M. LEŚKIEWICZ, W. LASOŃ. Pol. J. Pharmacol., 2000, 52, 359-365. Effects of antidepressants (desipramine, amitriptyline), anticonvulsants (phenytoin, diazepam, carbamazepine) and addictive drugs (amphetamine, morphine), used at a concentration of 100 µM on the conversion of [14C]-progesterone to 5alpha-pregnane-3,20-dione and allopregnanolone in slices of the frontal cortex and olfactory bulb from rat brain were studied. The synthesis of alpha-pregnane-3,20-dione and allopregnanolone was stronger in the olfactory bulb than in the frontal cortex. The biosynthesis of allopregnanolone in the frontal cortex was higher by 74, 109 and 187% when stimulated by amitriptyline, desipramine and carbamazepine, respectively, and, to a lesser degree, by phenytoin and morphine. Desipramine and morphine decreased the concentration of 5alpha-pregnane-3,20-dione. In the olfactory bulb, only carbamazepine enhanced allopregnanolone production, but none of the tested drugs had any effect on 5alpha-pregnane-3,20-dione synthesis. It is concluded that some psychotropic drugs may increase allopregnanolone synthesis by stimulating the activity of the enzyme, 3a-hydroxysteroid dehydrogenase, in the frontal cortex, and that this neurosteroid may be partly involved in the mechanism of action of the drugs under study. Key words: psychotropic drugs, allopregnanolone, 3alpha-hydroxysteroid dehydrogenase, frontal cortex, olfactory bulb, rats |
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