Summary
Meta-chlorophenylpiperazine inhibited serotonin and noradrenaline uptake by synaptosomes to the same extent with IC50 of 1.3×10−6 M and 5.8×10−6 M respectively. Dopamine uptake was lesss affected by meta-chlorophenylpiperazine (IC50 of 2.2×10−5 M). Unlike d-amphetamine and d-fenfluramine, the drug did not significantly increase monoamine release in synaptosomal preparations. On the other hand, metachlorophenylpiperazine showed an IC50 of 620 nM in displacing 3H-5HT binding to brain membranes. Meta-chlorophenylpiperazine produced a dose-dependent reduction of food intake and this effect was prevented by a pretreatment with methergoline, a serotonin antagonist. The effect of metachlorophenylpiperazine was not modified by an intraventricular injection of 6-hydroxydopamine, electrolytic lesions of nucleus medianus raphe or ventral noradrenergic bundle, nor by a pretreatment with penfluridol, propranolol or phentolamine. The data suggest that the decrease of food intake induced by metachlorophenylpiperazine depends on its ability to act as a serotonin agonist in the brain. The specificity of the effects on serotonin suggests that this compound could prove an important tool for studies aimed at elucidating the functional role of serotonin in the central nervous system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahlskog, J. E., Hoebel, B. G.: Overeating and obesity from damage to a noradrenergic system in the brain. Science 182, 166–169 (1973)
Bennett, J. P., Jr., Snyder, S. H.: Serotonin and lysergic acid diethylamide binding in rat brain membranes: Relationship to postsynaptic serotonin receptors. Mol. Pharmacol. 12, 373–389 (1976)
Breese, G. R., Traylor, T. D.: Depletion of brain noradrenaline and dopamine by 6-hydroxydopamine. Br. J. Pharmacol. 42, 88–99 (1971)
Chang, C. C.: A sensitive method for spectrophotofluorometric assay of catecholamines. Int. J. Neuropharmacol. 3, 643–649 (1964)
Curzon, G., Green, A. R.: Rapid method for the determination of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in small regions of rat brain. Br. J. Pharmacol. 39, 653–655 (1970)
Fuxe, K., Farnebo, L. O., Hamberger, B., Ogren, S. O.: On the “in vivo” and “in vitro” actions of fenfluramine and its derivatives on central monoamine neurons, especially 5-hydroxytryptamine neurons, and their relation to the anorectic activity of fenfluramine. Postgrad. Med. J. 51, Suppl. 1, 35–45 (1975)
Garattini, S.: Importance of serotonin for explaining the action of some anorectic agents. In: 2nd. International Congess on Obesity, Oct. 23–26, 1977, Washington D.C. (In press, 1979)
Garattini, S., Buczko, W., Jori, A., Samanin, R.: On the mechanism of action of fenfluramine. Postgrad. Med. J. 51, Suppl. 1, 27–35 (1975)
Garattini, S., de Gaetano, G., Samanin, R., Bernasconi, S., Roncaglioni, M. C.: Effects of trazodone on serotonin in the brain and platelets of the rat. Biochem. Pharmacol. 25, 13–16 (1976)
Ghezzi, D., Samanin, R., Bernasconi, S., Tognoni, G., Gerna, M., Garattini, S.: Effect of thymoleptics on fenfluramine-induced depletion of brain serotonin in rats. Eur. J. Pharmacol. 24, 205–210 (1973)
Glowinski, J.: Effects of amphetamine on various aspects of catecholamine metabolism in the central nervous system of the rat. In: Amphetamines and related compounds (E. Costa and S. Garattini, eds.), pp. 301–316. New York: Raven Press 1970
Gray, E. G., Whittaker, V. P.: The isolation of nerve endings from brain: An electron-microscopic study of cells fragments derived by homogenization and centrifugation. J. Anat. 96, 79–88 (1962)
Heikkila, R. E., Orlansky, H., Cohen, G.: Studies on the distinction between uptake inhibition and release of 3H-dopamine in rat brain tissue slices. Biochem. Pharmacol. 24, 847–852 (1975)
König, J. F. R., Klippel, R. A.: The rat brain: A stereotaxic atlas of the forebrain and lower parts of the brain stem. Baltimore: Williams and Wilkins 1963
Laverty, R., Taylor, K. M.: The fluorometric assay of catecholamines and related compounds: Improvements and extensions to the hydroxyindole technique. Anal. Biochem. 22, 269–279 (1968)
Mawson, C., Whittington, H.: Evaluation of the peripheral and central antagonistic activities against 5-hydroytryptamine of some new agents. Br. J. Pharmacol. 39, 223P (1970)
Mennini, T., Pataccini, R., Samanin, R.: Effect of narcotic analgesics on the uptake and release of serotonin in rat synaptosomal preparations. Br. J. Pharmacol. 64, 75–82 (1978)
Noble, E. P., Wurtman, R. J., Axelrod, J.: A simple and rapid method for injecting H3-norepinephrine into the lateral ventricle of the rat brain. Life Sci. 6, 281–291 (1967)
Raiteri, M., Angelini, F., Levi, G.: A simple apparatus for studying the release of neurotransmitters from synaptosomes Eur. J. Pharmacol. 25, 411–414 (1974)
Samanin, R., Ghezzi, D., Valzelli, L., Garattini, S.: The effects of selective lesioning of brain serotonin or catecholamine containing neurones on the anorectic activity of fenfluramine and amphetamine. Eur. J. Pharmacol. 19, 318–322 (1972)
Samanin, R., Bendotti, C., Candelaresi G., Garattini, S.: Specificity of serotoninergic involvement in the decrease of food intake induced by quipazine in the rat. Life Sci. 21, 1259–1266 (1977a)
Samanin, R., Bendotti, C., Bernasconi, S., Borroni, E., Garattini, S.: Role of brain monoamines in the anorectic activity of mazindol and d-amphetamine in the rat. Eur. J. Pharmacol. 43, 117–124 (1977b)
Samanin, R., Caccia, S., Borroni, E., Invernizzi, R., Pataccini, R., Mennini, T.: Further studies on the mechansism of serotonin-dependent anorexia in rats. Eur. J. Pharmacol. (1979a)
Samanin, R., Bernasconi, S., Borroni, E., Invernizzi, R., Carli, M., Garattini, S.: Behavioral and biochemical effects of equianorectic doses of various compounds in the rat. Arch. Int. Pharmacodyn. (1979b)
Ziance, R. J., Rutledge, C. O.: A comparison of the effects of fenfluramine and amphetamine on uptake, release and catabolism of norepinephrine in rat brain. J. Pharmacol. Exp. Ther. 180, 118–126 (1972)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Samanin, R., Mennini, T., Ferraris, A. et al. m-Chlorophenylpiperazine: A central serotonin agonist causing powerful anorexia in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 308, 159–163 (1979). https://doi.org/10.1007/BF00499059
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00499059