Pharmacological effects of
venlafaxine, a new antidepressant, given repeatedly, on the alpha
1-adrenergic, dopamine and serotonin systems
Maj J, Rogoz Z
Institute of Pharmacology,
Polish Academy of Sciences, Krakow, Poland.
J Neural Transm 1999; 106(2):197-211
ABSTRACT
Venlafaxine (VEN) is a representative of a new
class of antidepressants (SNRIs) which inhibit selectively the uptake of
serotonin and noradrenaline, but--in contrast to tricyclics--show no
affinity for neurotransmitter receptors. The present study was aimed at
determining whether repeated VEN (given twice daily for 14 days) induced
adaptive changes in the alpha 1-adrenergic, dopamine and serotonin systems,
similar to those reported by us earlier for tricyclic antidepressants.
The results indicate that VEN potentiates the clonidine-induced
aggressiveness and the methoxamine-induced exploratory hyperactivity, both
these effects being mediated by alpha 1-adrenoceptors. VEN increased
the hyperlocomotion induced by D-amphetamine and ()-7-OH-DPAT. Neither the
apomorphine and quinpirole hyperlocomotion, nor the apomorphine and
D-amphetamine stereotypies were changed. VEN did not affect the
behavioural syndrome induced by 8-OH-DPAT (a 5-HT1A effect), and decreased
both the head twitch reaction induced by L-5-HTP or ()DOI and the
hyperthermia induced by trifluoromethylphenylpiperazine, all those effects
being mediated by 5-HT2 receptors. Repeated VEN did not change the
hypothermia evoked by oxotremorine (a central cholinergic agonist). The
above results indicate that repeated VEN increases--as do tricyclics--the
responsiveness of alpha 1-adrenergic and dopaminergic (mainly D3) systems
and decreases the responsiveness of the 5-HT2 system. It may be
concluded that the lack of affinity for neurotransmitter receptors is of no
importance to the development of adaptive changes in the studied systems,
observed after repeated treatment.
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