Central antiserotonin action of amitriptyline.

Amitriptyline (AMI) was studied in rats snd mice in order to find out whether it had a central antiserotonin activity, previously demonstrated for doxepin - a compound chemically related to AMI. It was observed that AMI at low doses antagonized the head twitch response to L-5-hydroxytryptophan or 5-methoxytryptamine, as well as tryptamine-induced convulsions. In the hind limb flexor reflex preparation of the spinal rat AMI acted as a serotonin antagonist: when administered alone, it did not change the flexor reflex but prevented its stimulation induced by serotoninmimetics (LSD, quipazine, fenfluramine) not affecting that one evoked by noradrenalinemimetics (clinidine). At higher doses, AMI revealed a noradrenolytic activity. The results indicate that AMI, similarly as doxepin, has a central antiserotonin activity.