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Vol. 303, Issue 2, 815-822, November 2002
Department of Psychopharmacology, Institut de Recherches Servier,
Paris, France
Although certain antiparkinson agents interact with serotonin (5-HT)
receptors, little information is available concerning functional
actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT1A, h5-HT1B, and
h5-HT1D receptors [guanosine
5'-O-(3-[35S]thio)triphosphate
([35S]GTP
S) binding], and at h5-HT2A,
h5-HT2B, and h5-HT2C receptors (depletion of
membrane-bound [3H]phosphatydilinositol). All drugs
stimulated h5-HT1A receptors with efficacies (compared with
5-HT, 100%) ranging from modest (apomorphine, 35%) to high
(cabergoline, 93%). At h5-HT1B receptors, efficacies
varied from mild (terguride, 37%) to marked (cabergoline, 102%) and
potencies were modest (pEC50 values of 5.8-7.6):
h5-HT1D sites were activated with a similar range of
efficacies and greater potency (7.1-8.5). Piribedil and apomorphine
were inactive at h5-HT1B and h5-HT1D receptors.
At h5-HT2A receptors, terguride, lisuride, bromocriptine,
cabergoline, and pergolide displayed potent (7.6-8.8) agonist
properties (49-103%), whereas apomorphine and roxindole were
antagonists and piribedil was inactive. Only pergolide (113%/8.2) and
cabergoline (123%/8.6) displayed pronounced agonist properties at
h5-HT2B receptors. At 5-HT2C receptors, lisuride, bromocriptine, pergolide, and cabergoline were efficacious (75-96%) agonists, apomorphine and terguride were antagonists, and
piribedil was inactive. MDL100,907 and SB242,084, selective antagonists
at 5-HT2A and 5-HT2C receptors, respectively,
abolished these actions of pergolide, cabergoline, and bromocriptine.
In conclusion, antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes. Although all show modest (agonist) activity at
5-HT1A sites, their contrasting actions at
5-HT2A and 5-HT2C sites may be of particular
significance to their functional profiles in vivo.
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