TRANYLCYPROMINE DOES NOT ENHANCE THE EFFECTS OF AMITRIPTYLINE ON 5-HT2 RECEPTORS IN RAT CEREBRAL-CORTEX

The combination of amitriptyline (a tricyclic antidepressant) and tran ylcypromine (a monoamine oxidase inhibitor) has been reported to be ef fective for treatment of refractory depressed patients. In the study r eported here, this drug combination was compared with amitriptyline ad ministered alone on the number and affinity of 5-HT2 receptors in rat brain. Male Sprague-Dawley rats were given vehicle (distilled water), amitriptyline (3.5 mg/kg/day), or tranylcypromine and amitriptyline (0 .5 and 3.5 mg/kg/day, respectively) in combination subcutaneously via osmotic minipumps for 4, 10, or 28 days. A membrane fraction prepared from whole cortex was employed for studying binding to 5-HT2 receptors ([H-3] ketanserin as the radioligand). The combination of amitriptyli ne and tranylcypromine produced a small but significantly greater down -regulation (decrease in number) of 5-HT2 sites than did amitriptyline alone after 10 days of administration; at 4 and 28 days, both amitrip tyline and the drug combination had produced down-regulation, but ther e was not a significant difference between the two treatments. These d ata suggest that the antidepressant efficacy observed with this combin ation is not likely due to an enhanced effect on 5-HT2 receptors.