Studies on brain metabolism of biogenic amines.

Abstract

6 Nomifensine differs from the tricyclic antidepressants by virtue of its effect on the dopaminergic system.

Recent Investigations on the Mechanism of Action of Nomifensine

“…Studies from several groups using different methods have clearly dem onstrated that nomifensine is a monoamine uptake blocker resembling the tricyclic antidepressants [14,20,37,[41][42][43]54[. Table I shows our results from in vitro studies using synaptosomal fractions from rat hypothalamus and corpus striatum, respectively.…”

“…Crude synaptosomal fractions from rat brain (Wistar, 100-150 g) were obtained according to the method of Whittaker [56], Our methods for determining monoamine uptake were similar to those of Snyder and Coyle [48] and have been described in detail elsewhere [42,43], Uptake of 14C-NA(1 X 10-7 Affinal concentration; 55 mCi/mmol) was measured in synaptosomes from the hypothalamus using Krebs-Henseleit bicarbonate buffer (pH 7.4), containing 11 mM glucose, while phosphate buffer (pH 6.6) was used for studying the uptake of 3H-DA (1 X 10~7 M final concentration; 2.3 Ci/mmol) in synapto somes from the corpus striatum. Incubation time was 10 min with synaptosomes from hypothalamus, and 3 min with striatal synaptosomes.…”

“…The method used for studying drug effects on the release of DA from electrically stimulated brain slices is based on that of Farnebo and Hornberger [13] and has been described in detail elsewhere [43]. Slices from rat brain striatum were incubated for 30 min at 37 °C in a Krebs bicarbonate buffer (pH 7.4) with 3H-DA (1 X 10~7 M\ 2.7 Ci/mmol).…”

Effect of Two Indirectly Acting Dopamine Agonists on Prolactin Secretion in Normo- and Hyperprolactinemic Subjects: Comparison with the Effect of Nomifensine

“…Interestingly, nomifensine shares with amphetamine the property of inhibiting uptake me chanisms in DA synaptosomes and of releasing DA from neuronal stores [2]. In addition, nomifensine is a potent in hibitor of norepinephrine reuptake [21], Both drugs have a neuropharmacologic profile very similar to that of another amphetamine-like stimulant drug, i.e., methylphenidate, which also releases DA from neuronal stores and blocks its reuptake into nerve terminals [2,8]. Amineptine also has a similar neuropharmacologic profile; like nomifensine and methylphenidate it releases DA from neuronal stores and blocks DA reuptake [ 19].…”

A comparison of the pharmacodynamic profiles of nomifensine and amitriptyline in normal subjects.

“…Pharmacologically, it shares in many respects a profile similar to tricyclic antidepressants: however, nomifensine also influences dopaminergic mechanisms, acting as a dopamine (DA) agonist (Costall, Kelly & Naylor, 1975, Hoffman, 1977. It inhibits rat synaptosomal uptake of noradrenaline, DA and 5-hydroxytryptamine (5-HT) in vitro (Schacht, Leven & Backer, 1977), and has also been shown to inhibit the in vitro uptake of DA and 5-HT into human platelets . The incidence of anticholinergic side-effects was reportedly less in some studies in depressed patients (McClelland, Kerr & Littler, 1977) while in other studies such a difference was not significant (Forrest, Hewett & Nicholson, 1977).…”