Tranylcypromine does not enhance the effects of amitriptyline on 5-HT2 receptors in rat cerebral cortex

The combination of amitriptyline (a tricyclic antidepressant) and tranylcypromine (a monoamine oxidase inhibitor) has been reported to be effective for treatment of refractory depressed patients. In the study reported here, this drug combination was compared with amitriptyline administered 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 ([3H]ketanserin as the radioligand). The combination of amitriptyline 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 amitriptyline and the drug combination had produced down-regulation, but there was not a significant difference between the two treatments. These data suggest that the antidepressant efficacy observed with this combination is not likely due to an enhanced effect on 5-HT2 receptors.