Administration of the serotonin (5-HT) releasing compound p-chloroamphetamine (PCA; 2.5 mg/kg) induced potent analgesia in rats tested with the hot plate method. The analgesia was prevented by pretreatment with either of the 5-HT uptake inhibitors alaproclate (20 mg/kg) or fluoxetine (10 mg/kg). Taking into account that the noradrenergic uptake inhibitor desipramine in previous experiments failed to interfere with the effect of PCA, these results demonstrate that PCA selectively acts on 5-HT terminals. The analgesia was attenuated by administration of the 5-HT antagonists methiothepin (0.125-0.5 mg/kg) and danitracen (0.25-2.5 mg/kg) but not by a series of other 5-HT receptor antagonists or antagonists acting on noradrenergic, dopaminergic, GABAergic, histaminergic or muscarinic receptors. It is concluded that the analgesic effect of PCA is mediated via stimulation of a type of 5-HT receptors possibly belonging to the 5-HT-1 class. Further studies are, however, needed in order to firmly establish the relationship to any particular sub-type of 5-HT receptor as characterized in in vitro binding studies.

01 Jan 1985·PsychopharmacologyQ3 · MEDICINE

Serotonergic potentiation of muscarinic agonist evoked tremor and salivation in rat and mouse

Q3 · MEDICINE

Article

Author: S. O. Ogren ; T. Bartfai ; S. Carlsson

The dose-effect of oxotremorine upon the onset, duration and magnitude of tremor and salivation was studied in both mice and rats. The threshold doses of oxotremorine (SC) for eliciting tremor were above 50 micrograms/kg in mice and above 150 micrograms/kg in rats and the threshold doses for eliciting salivation were above 75 micrograms/kg in mice and above 200 micrograms/kg in rats. Alaproclate, a nontricyclic 5-HT uptake inhibitor, when injected 30 min prior to the administration of the cholinergic agonist, produced a dose-dependent enhancement of tremor and salivation in both rats and mice. Alaproclate itself did not produce these effects in the absence of a muscarinic cholinergic stimulant such as oxotremorine, arecoline or the acetylcholine esterase inhibitor physostigmine. Both salivation and tremor could be fully blocked by atropine at any dose of the cholinergic stimulant and of alaproclate used. The potentiating effects of alaproclate on salivation and tremor could also be blocked by two serotonin receptor antagonists, metitepine and danitracen, but not by metergoline or cinanserin. Other compounds which inhibit the uptake of 5-HT such as fluoxetine, citalopram, norzimeldine, zimeldine and the non-tricyclic antidepressant, iprindol, did not enhance the cholinergic agonist induced tremor or salivation under the same conditions as did alaproclate. It is suggested that alaproclate exerts the potentiating effect at a hitherto undefined serotonergic receptor site.

01 Jun 1982·Journal of Neural Transmission

Neurochemical effects of danitracen (WA-355): Mechanism of action

Article

Author: P. C. Dandiya ; N. K. Gurbani ; H. J. Hrishi Keshavan

Danitracen lowered serotonin levels in the cerebrum, cerebellum, medulla and the whole brain. The drug did not appear to affect the concentration of 5-HIAA except in the cerebellum where there was a considerable depletion. Danitracen pretreatment led to a lowering in the 5-HIAA levels in the whole brain and decreased NE levels in apomorphine and amphetamine treated rats. The findings indicate that the mechanism of action of danitracen also involves noradrenergic neurons along with a possible increase in the metabolism.

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