Citalopram: a new potent inhibitor of serotonin (5-HT) uptake with central 5-HT-mimetic properties.

Citalopram (1--16 mg/kg), but not amitriptyline, clomipramine, imipramine or zimelidine, stimulated the hind limb flexor reflex in the spinal rat. This stimulatory effect was abolished by serotonin (5-HT) receptor blocking agents (cyproheptadine, metergoline) and prevented ty p-chlorophenylalanine, an inhibitor of 5-HT synthesis. Citalopram (20 mg/kg), similarly but more strongly than clomipramine (20 mg/kg), prevented both fenfluramine- and p-chloroamphetamine-induced hyperthermia in rats kept at 28 degrees C. In contrast to amitriptyline and imipramine, citalopram did not reduce the number of quipazine-induced head twitches in rats (ID50 greater than 50 mg/kg). Also, unlike the above mentioned antidepressants, it did not antagonize, but rather potentiated the 5-HT-mediated rise in blood pressure in pithed rats. The results obtained indicate that, unlike the presently known inhibitors of 5-HT uptake, citalopram considerably potentiates serotonergic transmission, possibly by producing very strong inhibition of uptake without simultaneous blockade of the postsynaptic 5-HT receptors.