Inhibition of catechol-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
N B
NB
IRCCS Santa Lucia and Clinica Neurologica, Università di Tor Vergata, Roma, Italy. Mercurin@med.uniroma2.it
Federici
M
M
Bernardi
G
G
D000818:Animals; D001577:Benzophenones / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010300:Parkinson Disease / Q000201:enzymology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013331:Strychnine / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000201:enzymology*; D013469:Sulpiride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D000077867:Tolcapone; D017557:Ventral Tegmental Area / Q000166:cytology / Q000201:enzymology*
D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D004298:Dopamine; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D018684:Glycine Agents; D007980:Levodopa; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D013331:Strychnine; D013469:Sulpiride; D000077867:Tolcapone; C066430:CGP 35348