Catechol Omethyltransferase inhibitors

An increase in the functional monoamines NE, DA, and 5HT can precipitate mania or rapid-cycling in an estimated 20-30% of affectively ill patients. A strong association between velo-cardio-facial syndrome (VCFS) patients diagnosed with rapid-cycling bipolar disorder, and an allele encoding the low enzyme activity catechol-O-methyltransferase variant (COMT L) has been identified.43 Between 85% and 90% of VCFS patients are hemizygous for COMT. There is nearly an equal distribution of L and H alleles in Caucasians. Individuals with low-activity allele (COMT LL) would be expected to have higher levels of transynaptic catecholamines due to a reduced COMT degradation of NE and DA. COMT inhibitors (entacapone (40) and tolcapone (41)) could therefore be beneficial as adjuncts to L-dopa not only in Parkinson's disease but also in the coincident depressive illness associated with rapid cycling.

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