Dopamine antagonist

Activity is apparently retained when the aromatic amino group is deleted. Brominadon of acid 148 followed by reaction of the product (149), as its acid chloride, with the (S)-(-)-amino-methylpyrrolidine 150, gives the dopamine antagonist, remoxipride (151) [37] with (S)-configu-ration. 

The synthesis of a benzamide with a somewhat more complex side chain starts by condensation of acid 144 with racemic cis-aminopiperidine 152. Removal of the benzyl group of 153 by hydrogenolysis gives the secondary amine 154. Alkylation on nitrogen with the halide 155 gives finally the dopamine antagonist, cisapride (156) [38,39]. 

Atypical antipsychotic diugs Novel antipsychotic diugs serotonin/dopamine antagonists 5HT2A/D2 antagonists. 

The reinforeing properties of psychomotor stimulants have also been linked to the aetivation of eentral dopamine neurons and their postsynaptie reeep-tors. When the synthesis of eatecholamines is inhibited by administering alpha-methyl-para-tyrosine, an attenuation of the subjective effeets of euphoria assoeiated with psyehomotor stimulants oeeurs in man (Jonsson et al. 1971), and a bloekade of the reinforeing effects of methamphetamine occurs in animals (Pickens et al. 1968). Furthermore, low doses of dopamine antagonists will increase response rates for intravenous injections of h-amphetamine (Risner and Jones 1976 Yokel and Wise 1975 Yokel and Wise 1976). 

Woolverton, W.L. Effects of a D1 and D2 dopamine antagonist on the self-administration of cocaine and piribedil by rhesus monkeys. 

I think the fact that haloperidol and all the dopamine antagonists work doesn t bring much clarity to the situation. I think it muddies the water. 

QUESTION How do you imagine that both a receptor antagonist and an uptake inhibitor would block the effects It would seem that if dopamine is involved, it would either be acting on a membrane receptor or inside, but not both. I would also like to ask a more specific question. You showed that the alpha MT protected effect could be reversed by dopa. And I think you imagined that that was because of dopamine formation. But have you tried dopamine agonists to see if they would antagonize either the protective effect of alpha methyltyrosine or, particularly, the protective effect of the dopamine antagonists to try to verily that those protective effects really have to do with blockade of a dopamine receptor as opposed to some other possibility ... 

Ujike, H., Onoue, T., Akiyama, K., Hamamura, T., Otsuki, S. Effects of selective D-l and D-2 dopamine antagonists on development of methamphetamine-induced behavioral sensitization. Psychopharmacology. 98 89, 1989. 

Hubner C., Moreton J. Effect of selective I ), and D2 dopamine antagonists on cocaine self-administration in the rat. Psychopharmacology. 105 151, 1991. 

Koob G., Le H., Creese I. The Dj dopamine antagonist SCH 23390 increases cocaine self-administration in the rat. Neurosci. Lett. 79 315, 1987. 

Metoclopramide, administered at doses higher than those required to inhibit apomorphine-induced emesis, was more effective than haloperidol in antagonizing cisplatin-induced emesis in dogs [80]. This was observed despite the fact that metoclopramide was considerably weaker than haloperidol as a D2-dopamine antagonist [43]. Subsequently, antiemetic efficacy of metoclopramide administered at high doses has been reported in cancer patients... 

It had been reported that 5-HT and 2-Me-5-HT released DA in striatal slices [112]. The functional importance of this response is unknown, because the D2-dopamine antagonists are not efficient antiemetics against radiation- or chemotherapy-induced emesis. 

Antidepressant effects Hypericum has been shown to have antidepressant effects in several animal models. An extract fraction high in naphthodianthrones showed antidepressant effects in the forced-swim test, and was attenuated by a dopamine antagonist (sulpiride) (Butterweck et... 

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