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Inhibition of cathecol-O-methyltransferase (COMT) in the brain does not affect the action of dopamine and levodopa: an in vitro electrophysiological evidence from rat mesencephalic dopamine neurons. In order to study whether the membrane hyperpolarization and firing inhibition caused by dopamine and levodopa on rat midbrain dopamine cells are affected by the inhibition of brain catechol-O-methyl-transferase (COMT), intracellular electrophysiological recordings were made from these neurons maintained in vitro. Here we report that a treatment of the cerebral tissue with tolcapone, a central and peripheral inhibitor of COMT, does not change the membrane responses of midbrain dopamine neurons to dopamine and levodopa. The lack of modification of the dopaminergic effects by tolcapone suggests that the pharmacological inhibition of intracerebral COMT does not have detectable action on dopamine neurotransmission. Therefore, the therapeutic action of tolcapone in Parkinson's disease, might be dependent on the reduction of COMT activity in the extracerebral tissue. Mercuri NB, Federici M, Bernardi G J Neural Transm 1999;106(11-12):1135-40 IRCCS Santa Lucia and Clinica Neurologica, Universita di Tor Vergata, Roma, Italy. <[log in to unmask]> PMID: 10651109, UI: 20114531 <http://www.ncbi.nlm.nih.gov/PubMed/> janet paterson 52 now / 41 dx / 37 onset a new voice: http://www.geocities.com/janet313/ 613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0