L. Arborelius et al., The 5-HT1A receptor antagonist robalzotan completely reverses citalopram-induced inhibition of serotonergic cell firing, EUR J PHARM, 382(2), 1999, pp. 133-138
5-HT1A receptor antagonists have been suggested to increase the efficacy of
selective serotonin (5-hydroxytrypramine; 5-HT) reuptake inhibitors in the
treatment of depression by enhancing the increase in brain 5-HT induced by
5-HT reuptake blockade. Here, the novel 5-HT1A receptor antagonist robalzo
tan [( R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-ca
rboxamide hydrogen (2R, 3R) tartrate monohydrate] (12.5, 25, 50, 100 mu g/k
g, i.v.) was found to completely reverse the acute inhibitory effect of cit
alopram (300 mu g/kg i.v.) or paroxetine (100 mu g/kg, i.v.) on the activit
y of 5-HT neurons in the dorsal raphe nucleus in rats. Robalzotan (5, 50 mu
g/kg, i.v.) by itself increased the firing rate of the majority of 5-HT ce
lls studied. The present results suggest that robalzotan may indeed augment
the increases in 5-HT output induced by selective 5-HT reuptake inhibitors
by antagonizing the feedback inhibition of 5-HT cell firing produced by su
ch drugs. Thus, robalzotan may be effective by enhancing the action of sele
ctive 5-HT reuptake inhibitors or as monotherapy in the treatment of depres
sion. (C) 1999 Elsevier Science B.V. All rights reserved.