Abstract
In a double blind, placebo-controlled study the effects of daily oral administration of 3-cyano-imipramine on the 3H-serotonin uptake capacity of platelets were investigated in healthy volunteers. The initial dose was 1 mg, rising to 3 mg daily for 7 days. A rapid and profound inhibition of 3H-serotonin uptake was observed in platelets isolated from the treated subjects. During repeated administration, uptake was reduced to less than 10% of pre-drug values. Five days after the final dose uptake had only partially recovered, to 53% of pre-drug values. A similar inhibition profile was observed when serum from the treated subjects was incubated with normal platelets and 3H-serotonin. The results establish 3-cyano-imipramine as a potent inhibitor of platelet serotonin uptake in humans.
This is a preview of subscription content, log in via an institution to check access.
References
Gordon JL, Olverman JJ (1978) 5-Hydroxytryptamine and dopamine transport by rat and human blood platelets. Br J Pharmacol 62:219–226
Haefely W, Schaffner R, Burkard W, Da Prada M, Keller HH, Polc P, Richards JG (1978) Ro 11-2465, a potent and selective inhibitor of 5-hydroxytryptamine uptake. 11th C.I.N.P. Congress Abstracts 95
Kenny M, Lenehan TJ, Lambe R, Darragh A, Brick I, Omer LMO (1983) Effects of a single oral dose of 3-cyano-imipramine on serotonin uptake and content of platelets in healthy volunteers. Psychopharmacology 79:304–307
Lenehan T, Omer LMO, Darragh A (1981a) Effect of Ro 11-2465, a new psychoactive agent on the uptake of serotonin by human platelets — in vitro determination of the IC50. Arch Int Pharmacodyn Ther 249:147–152
Lenehan T, Omer LMO, Kenny M, Lambe R, Darragh A (1981b) The effects of multiple rising doses of Ro 11-24565 (serotonin uptake inhibitor) on serotonin content of human platelets. Psychopharmacology 74:1–3
Lingjaerde O (1979) Inhibition of platelet uptake of serotonin in plasma from patients treated with clomipramine and amitriptyline. Eur J Clin Pharmacol 15:335–340
Pletscher A (1978) Platelets as models for monoaminergic neurons. In: Youdim MBH (ed) Essays in neurochemistry and neuropharmacology, vol 3. Wiley, London, p 49
Stahl SM, Meltzer HY (1978) A kinetic and pharmacological analysis of 5-hydroxytryptamine transport by human platelets and platelet storage granules: comparison with central serotionergic neurons. J Pharmacol Exp Ther 205:118–132
Todrick A, Tait AC (1969) The inhibition of human platelet 5-hydroxytryptamine uptake by tricyclic antidepressive drugs. The relation between structure and potency. J Pharm Pharmacol 21:751–762
Tuomisto J (1974) A new modification for styding 5-HT uptake by blood platelets: a re-evaluation of tricyclic antidepressants as uptake inhibitors. J Pharmacol 26:92–100
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lenehan, T.J., Kenny, M., Omer, L.M.O. et al. Platelet uptake of serotonin following repeated administration of 3-cyano-imipramine to healthy volunteers. Psychopharmacology 81, 357–358 (1983). https://doi.org/10.1007/BF00427578
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00427578