Abstract
Citalopram (1–16 mg/kg), but not amitriptyline, clomipramine, imipramine or zimelidine, stimulated the hind limb flexor reflex in the spinal rat. This stimulatory effect was abolished by serotonin (5-HT) receptor blocking agents (cyproheptadine, metergoline) and prevented by p-chlorophenylalanine, an inhibitor of 5-HT synthesis. Citalopram (20 mg/kg), similarly but more strongly than clomipramine (20 mg/kg), prevented both fenfluramine- and p-chloroamphetamine-induced hyperthermia in rats kept at 28°C. In contrast to amitriptyline and imipramine, citalopram did not reduce the number of quipazine-induced head twitches in rats (ID50>50 mg/kg). Also, unlike the above mentioned antidepressants, it did not antagonize, but rather potentiated the 5-HT-mediated rise in blood pressure in pithed rats. The results obtained indicate that, unlike the presently known inhibitors of 5-HT uptake, citalopram considerably potentiates serotonergic transmission, possibly by producing very strong inhibition of uptake without simultaneous blockade of the postsynaptic 5-HT receptors.
Similar content being viewed by others
References
Bigler AJ, Bøgesø KP, Toft A, Hansen V (1977) Quantitative structure-activity relationships in a series of selective 5-HT uptake inhibitors. Eur J Med Chem — Chimica Therapeutica 12:289–295
Frey HH (1975) Hyperthermia induced by amphetamine, p-chloroamphetamine and fenfluramine in the rat. Pharmacology 13:163–176
Ghose K, Gupta R, Coppen A, Lund J (1977) Antidepressant evaluation and the pharmacological actions of FG 4963 in depressive patients. Eur J Pharmacol 42:31–37
Gillespie JS, Maclaren A, Pollock D (1970) A method of stimulating different segments of the autonomic outflow from the spinal column to various organs in the pithed cat and rat. Br J Pharmacol 40:257–267
Hyttel J (1977) Neurochemical characterization of a new potent and selective serotonin uptake inhibitor: Lu 10–171. Psychopharmacology 51:225–233
Litchfield JT, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96:96–113
Maj J, Lewandowska A, Rawŀów A (1979) Central antiserotonin action of amitriptyline. Pharmakopsychiat Neuropsychopharmakol 12:281–285
Maj J, Palider W, Baran L (1976) The effects of serotonergic and antiserotonergic drugs on the flexor reflex of spinal rat: a proposed model to evaluate the action on the central serotonin receptor. J Neural Transm 38:131–147
Ögren S-O, Fuxe K, Agnati LF, Gustafsson JA, Jonsson G, Holm AC (1979) Re-evaluation of the indoleamine hypothesis of depression. Evidence for a reduction of functional activity of central 5-HT systems by antidepressant drugs. J Neural Transm 46:85–103
Pedersen OL, Bjerre M, Kragh-Sørensen P, Kristensen CB, Overø KF (1980) Clinical evaluation of citalopram (Lu 10–171) — a specific 5-HT uptake inhibitor. Abstracts of the 12th CINP Congress, Göteborg, 22–26 June 1980. In: Radouco-Thomas C, Garcin F (eds) Pergamon Press, Oxford, p 229, abs 408
Petersen EN, Olsson S-O, Squires RF (1977) Effects of 5-HT uptake inhibitors on the pressor response to 5-HT in the pithed rat. The significance of the 5-HT blocking property. Eur J Pharmacol 43:209–215
Sulpizio A, Fowler PJ, Macko E (1978) Antagonism of fenfluramine-induced hyperthermia: a measure of central serotonin inhibition. Life Sci 22:1439–1446
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pawłowski, L., Ruczynska, J. & Górka, Z. Citalopram: A new potent inhibitor of serotonin (5-HT) uptake with central 5-HT-mimetic properties. Psychopharmacology 74, 161–165 (1981). https://doi.org/10.1007/BF00432685
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00432685