The Effect of Iproniazid and Imipramine on the Blood Platelet 5‐hydroxytryptamine Level in Man

Abstract

Observations are reported on the blood platelet 5-hydroxytryptamine content of six patients receiving imipramine, N-(y-dimethylaminopropyl)-iminodibenzyl hydrochloride. The response was a fall to a level of one-sixth of the original in three weeks, with little change thereafter. This is in sharp contrast to the action of iproniazid which caused a rise of some 2000% in the blood platelet 5-hydroxytryptamine level over the same period. Imipramine in a concentration of 1 mg./ml. had no inhibitory action on 5-hydroxytryptophan decarboxylase; 8 0 [kg./ml. of imipramine suppressed two-thirds of the in vitro uptake of 5-hydroxytryptamine (2-5 [tg./ml.)by normal human platelets.The recently developed pharmacological approach to the treatment of disordered mental states, particularly schizophrenia, with the so-called tranquillizing or ataractic drugs has undoubtedly achieved results (Brill and Patton, 1957), although the individual response is unpredictable and the mode of action is still not clear. Nevertheless, the degree of success has been sufficient to cause the adoption of a similar approach to the treatment of the other major functional psychosis, the manic-depressive syndrome. Of the two aspects of this illness, the depressive is the more frequent in the ratio of 10 to 1 and therefore calls for more urgent attack.

Release of 5-hydroxytryptamine from blood platelets

“…It was reported by Marshall, Stirling, Tait & Todrick (1960) that, during imipramine treatment, the ~-H T content of platelets decreases in three weeks to about one-sixth of the original level. These authors also demonstrated that imipramine in vitro prevents the uptake of ~-H T by human platelets.…”

An intercalation mechanism as a mode of action exerted by psychotropic drugs: results of altered phospholipid substrate availabilities in membranes?

“…The plasma membrane uptake requires extracellular anions, particularly chloride [102,[106][107][108], and has since 1960 been known to be inhibited by tricyclic antidepressants, such as IMI [116]. Later, other antidepressants such as amitriptyline (AMI) [38], nucleotide triphosphate (NTP) [113], and citalopram (CTM) [1] (which have been used in the papers cited in the present review) and many other drugs have also been shown to inhibit serotonin uptake in platelets.…”

Drug‐induced Changes in the Concentration of 5‐or Indolyl Compounds in Cerebrospinal Fluid and Caudate Nucleus

“…Effect of imipramine on the concentration of 5-OR indolyl compounds in the cerebrospinal fluid Marshall, Stirling, Tait & Todrick (1960) have demonstrated that imipramine produced a fall in the concentration of 5-hydroxytryptamine in the blood platelets in man. A reduction to about 50% of control levels was observed after this drug had been administered daily for 5 days.…”