09.06.1 Inactivation by Metabolism

A drug used to inhibit the metabolism of a neurotransmitter is entacapone, which is used to increase the levels of dopamine in Parkinson’s disease. Parkinson’s disease is a progressive disease, which means there is a progressive loss of dopaminergic neurones. The dopaminergic neurons are needed to convert the L-DOPA to dopamine. Thus, with a decreasing number of dopaminergic neurones present, there is decreasing ability of dopaminergic neurones to convert L-DOPA to dopamine. Catechol-O-methyl-transferase (COMT) is one of the enzymes involved in the metabolism of dopamine. In the periphery, catechol-O-methyl-transferase also metabolises L-DOPA, and this metabolism leads to inactivation of the L-DOPA. Entacapone is an inhibitor of catechol-O-methyl-transferase. In the periphery, the ability of entacapone to inhibit the inactivation of L-DOPA leads to more L-DOPA being available to be transported into the central nervous system. In the central nervous system, entacapone lead to increased levels of dopamine by preventing its metabolism by entacapone.