Tranylcypromine, but not moclobemide, prolongs the inhibitory action of dopamine on midbrain dopaminergic neurons: an in vitro electrophysiological study.
The degradation of dopamine by monoamine oxidase (MAO) enzymes plays an important role in the function of dopamine receptors in the central nervous system. Accordingly, it has already been reported that the blockade of MAO by specific inhibitors prolongs the effects of dopamine on its receptors. By using intracellular electrophysiological recordings, here we report that the irreversible MAO A and B inhibitor tranylcypromine, but not the reversible MAO A inhibitor moclobemide, potentiates DA responses in rat midbrain dopaminergic neurones maintained in vitro. Moclobemide was not effective even when the MAO B enzymes were additionally blocked by the MAOI deprenyl. Thus, our electrophysiological findings confirm that the degradation DA is very important to control the effects of this catecholamine at a cellular level. Furthermore, they demonstrate that tranylcypromine potentiates DA neurotransmission while moclobemide is devoid of dopaminergic action in an in vitro condition. The phenomena reported above support the hypothesis that part of the antidepressant and antiparkinsonian effects of tranylcypromine depend on an action on DA transmission.
Mercuri
N B
NB
IRCCS Santa Lucia and Clinica Neurologica, Università di Tor Vergata, Roma, Italy. Mercurin@med.uniroma2.it
Federici
M
M
Marinelli
S
S
Bernardi
G
G
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D020912:Moclobemide / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013469:Sulpiride / Q000494:pharmacology; D014191:Tranylcypromine / Q000494:pharmacology*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D008996:Monoamine Oxidase Inhibitors; D014191:Tranylcypromine; D013469:Sulpiride; D020912:Moclobemide; D004298:Dopamine