This article will review the various agents affecting the central nervous system (CNS) such as the analgesics, antidepressants, anticonvulsants, antipsychotics, and benzodiazepines. Most of the research in pharmacogenetics with the CNS agents have been conducted in the antidepressants. The cytochrome 450 IID6 isozyme system has been shown to influence the disposition of the antidepressants and antipsychotics. Amitriptyline metabolism to nortriptyline and nortriptyline conversion to its 10-OH metabolite were shown to be influenced by the IID6 isozyme. Interestingly, imipramine metabolism to desipramine is only partially related to the IID6 isozyme. Biotransformation of imipramine to its 2-OH metabolite was shown to be affected by the IID6 isozyme, but its metabolism to the 10-OH remains to be investigated. Of the antipsychotic drugs, haloperidol and thioridazine are two agents most studied. Haloperidol is converted to a reduced metabolite via a ketone reductase enzyme. The reduced metabolite is oxidized back to Haloperidol. This oxidation pathway was reported to be affected by the IID6 isozyme. Thioridazine metabolism to mesoridazine and conversion of codeine to morphine appear to be also influenced by CP-450 IID6. Other 450 isozymes are reported to be involved with other CNS agents.
EFFECTS OF DILTIAZEM ON DOPAMINE RELEASE IN THE CENTRAL NERVOUS SYSTEM OF SPONTANEOUSLY HYPERTENSIVE RATS
