Summary
Effects of nomifensine (8-amino-1, 2, 3, 4-tetrahydro-2-methyl-4-phenyl-isoquinoline) (NF), an antidepressant drug which inhibits dopamine uptake, on central serotonergic structures were studied in rats. NF affects of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid levels in the whole brain as well as in the separate rat brain structures. The 5-HT turnover is decreased in the whole brain and the striatum but increased in the midbrain and the hippocamp as judged from experiments with tryptophan hydroxylase inhibitor,α-propyldopacetamide. Pretreatment with dopamine-receptor blocking agent, spiperone, antagonized the increase of 5-HT turnover rate in brain regions mentioned above.
NF stimulates the hind limb flexor reflex of spinal rat, a preparation regarded as a model for evaluation of drug action on central 5-HT neurons. This stimulatory effect was antagonized by cyproheptadine, by reserpine and imipramine. The obtained results indicate that NF activates central 5-HT neurons both directly and indirectly, via stimulation of dopamine receptors as described previously for other dopamine agonists.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andén, N.-E.: Effect of amphetamine and some other drugs on central catecholamine mechanisms. Symposium on amphetamines and releated compounds (Costa, E., Garattini, S., eds.), pp. 447–462. North-Holland Publ. Co. 1970.
Andén, N.-E., Corrodi, H., Fuxe, K.: Turnover studies using synthesis inhibition. In: Metabolism of Amines in the Brain (Hooper, G., ed.), p. 38. London: Macmillan. 1969.
Angst, J., Koukkou, M., Bleuler-Herzog, M., Martens, H.: Ergebnisse eines offenen und eines Doppelblindversuches von Nomifensin im Vergleich zu Imipramin. Arch. Psychiat. Nervenkr.219, 265–276 (1974).
Braestrup, C., Scheel-Krüger, J.: Methylphenidate-like effects of the new antidepressant drug nomifensine (Hoe 984). Eur. J. Pharmacol.38, 305–312 (1976).
Carlsson, A., Kehr, W., Lindqvist, M.: Agonist-antagonist interaction on dopamine receptors in brain, as reflected in the rates of tyrosine and tryptophan hydroxylation. Proc. Vth International Symposium on Parkinson's Disease, Vienna, September 17–20, 1975 (in press).
Corrodi, H., Fuxe, K.: The effect of imipramine on central monoamine neurons. J. Pharm. Pharmacol.20, 230–231 (1968).
Corrodi, H., Fuxe, K.: Decreased turnover in central 5-HT nerve terminals induced by antidepressant drugs of the imipramine type. Eur. J. Pharmacol.7, 56–59 (1969).
Costall, B., Kelly, D. M., Naylor, R. J.: Nomifensine: a potent dopaminergic agonist of antiparkinson potential. Psychopharmacologia (Berl.)41, 153–164 (1975).
Eckmann, F.: Klinische Untersuchungen mit dem Antidepressivum Nomifensin. In: Zur Systematik, Provokation und Therapie depressiver Psychosen, 2. Internationales Symposium in Graz (Walcher, W., ed.). Wien: 1974.
Gerhards, H. J., Carenzi, A., Costa, E.: Effect of nomifensine on motor activity, dopamine turnover rate and cyclic 3′ 5′-adenosine monophosphate concentrations of rat striatum. Naunyn-Schmiedeberg's Arch. Pharmacol.286, 49–63 (1974).
Grabowska, M.: The influence of apomorphine on brain sreotonin turnover rate. Pharmacol. Biochem. Behav.3, 589–591 (1975).
Grabowska, M., Andén, N.-E.: Apomorphine in the rat nucleus accumbens: effects on the synthesis of 5-hydroxytryptamine and noradrenaline, the motor activity and the body temperature. J. Neural Transm.38, 1–8 (1976).
Grabowska, M., Antkiewicz, L., Maj, J., Michaluk, J.: Apomorphine and central serotonin neurons. Pol. J. Pharmacol. Pharm.25, 29–39 (1973).
Grabowska, M., Przewlocki, R., Śmialowska, M.: On the direct or indirect influence of apomorphine on central serotonin neurons. J. Pharm. Pharmacol.28, 64–65 (1976).
Hoffmann, J.: 8-amino-2-methyl-4-phenyl-1, 2, 3, 4-tetrahydroisoquinoline, a new antidepressant. Arzneim.-Forsch.23, 45–50 (1973).
Hunt, P., Kannengiesser, M. H., Raynaud, J. P.: Nomifensine: a new potent inhibitor of dopamine uptake into synaptosomes from rat brain corpus striatum. J. Pharm. Pharmacol.26, 370–371 (1974).
Maickel, R. P., Cox, R. H., jr., Saillant, J., Miller, F. P.: A method for the determination of serotonin and norepinephrine in discrete areas of rat brain. Int. J. Neuropharmac.7, 275–281 (1968).
Maj, J.: The influence of dopaminergic agents on serotonin neurons. Antipsychotic drugs, pharmacodynamics and pharmacokinetics (Sedvall, G., Uvnas, B., Zotterman, J., eds.), pp. 235–241. Oxford: Pergamon Press. 1975.
Maj, J., Palider, W., Baran, L.: 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 (1976).
Miller, F. P., Cox, R. H., jr., Snodgrass, W. R., Maickel, R. P.: Comparative effects of p-chlorophenylalanine, p-chloroamphetamine and p-chloro-mmethylamphetamine on rat brain norepinephrine, serotonin and 5-hydroxyindole-3-acetic acid. Biochem. Pharmac.19, 435–442 (1970).
Riezen, H. van: Different central effects of 5-HT antagonists mianserine and cyproheptadine. Arch. Int. Pharmacodyn. Thér.198, 256–269 (1972).
Samanin, R., Bernasconi, S., Garattini, S.: The effect of nomifensine on the depletion of brain serotonin and catecholamines induced respectively by fenfluramine and 6-hydroxydopamine in rats. Eur. J. Pharmacol.34, 377–380 (1975).
Schacht, U., Heptner, W.: Effect of nomifensine (Hoe 984), a new antidepressant, on uptake of noradrenaline and serotonin and on release of noradrenaline in rat brain synaptosomes. Biochem. Pharmacol.23, 3413–3422 (1974).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mogilnicka, E., Klimek, V. & Golembiowska-Nikitin, K. Effect of nomifensine on central 5-hydroxytryptamine neurons. J. Neural Transmission 40, 195–204 (1977). https://doi.org/10.1007/BF01300134
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01300134