ROXINDOLE, A DOPAMINE AUTORECEPTOR AGONIST WITH A POTENTIAL ANTIDEPRESSANT ACTIVITY .2. EFFECTS ON THE 5-HYDROXYTRYPTAMINE SYSTEM

Roxindole (ROX) (EMD 49980, yl-1,2,3,6-tetrahydropyridyl(1))-butyl(1)] -indole, mesylate), a potent selective agonist of presynaptic dopamine receptors with clinical antipsychotic and antidepressant activity, wa s studied pharmacologically in rats (male Wistar) and mice (male Albin o Swiss) with respect to its influence on the central 5-hydroxytryptam ine (5-HT) system, ROX did not induce the 5-HT1A syndrome (flat body a nd forepaw treading) in rats, but partly antagonized the syndrome evok ed by 8-OH-DPAT. The 8-OH-DPAT-induced hypothermia in mice (a 5-HT1A e ffect) was not inhibited by ROX. The drug evoked hypothermia, which wa s antagonized by pindolol, but not by (+)-WAY-100135. ROX did not inhi bit the m-chlorophenylpiperazine-induced hypothermia in mice (a 5-HT1B effect), or the exploratory hypoactivity in rats (a 5-HT1C effect). H ead twitches induced by a low dose of L-5-HTP were potentiated by ROX, whereas those induced by its higher dose were antagonized. ROX also a ntagonized the hyperthermia induced by fenfluramine or trifluoromethyl phenylpiperazine at a high ambient temperature in rats (a 5-HT2A effec t). The results obtained indicate that ROX inhibits 5-HT uptake and sh ows 5-HT2A antagonistic and probably a 5-HT1B agonistic activities.