Cytochrome P450 in the Central Nervous System

Abstract

The brain is a major target for the action of steroids. These molecules regulate many aspects of brain function, including imprinting of sexual behavior (1), learning and memory (2), and mood and sleep/wakefulness (3). They are also thought to modulate neurodegenerative processes (4,5). The brain is, of course, also the target of many pharmaceutical agents, fatty acid metabolites, and organic solvents. Synthesis and degradation of steroid hormones, as well as the activation and inactivation of therapeutic agents and fatty acids involve several members of the cytochrome P450 super gene family (6,7). P450s are abundant in the adrenals, gonads, and liver, however, when measurable, most P450s are expressed at very low levels in the brain (8). The capacity of the brain to metabolize pharmaceuticals is so low that it is most unlikely that P450 in the brain plays any role in the overall clearance of pharmaceuticals from the body. However, those P450s that are selectively localized at high concentrations in limited numbers of brain cells, can play important roles in the physiology, pharmacology, and toxicology of those cells.