Significance of dopamine metabolites in the evaluation of drugs acting on dopaminergic neurons.
ABSTRACT The effect of various drugs was studied on 3-methoxytyramine (3-MT) concentrations in rat striatum. The drugs were chosen for their ability to interfere with the dopaminergic system at different levels. Dopamine (DA) acidic metabolites, i.e. homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), were also measured. Changes of 3-MT, unlike those of DOPAC and HVA, seem to reflect the functional activity of dopaminergic neurons. In fact drugs believed to increase or decrease DA content in the synaptic cleft produce predictable changes of striatal 3-MT. Thus cocaine, nomifensine and d-amphetamine increase 3-MT concentrations while gamma-butyrolactone, alpha-methyltyrosine and apomorphine decrease it.
- Foundations of Chemistry 05/2003;
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ABSTRACT: AE37F, a new aminotetrahydrofuranic derivative, exhibited, at 10-30 mg/Kg (po) or 1-10 mg/Kg (ip), antagonism of tonic convulsions, induced by pentetrazole (130 mg/Kg, ip), and of forced swin immobility, in mice. At these doses AE37F induced a considerable (100-250%) increase of serotonin (5-HT) and its main metabolite, 5-hydroxyindolacetic acid (5-HIAA), in the rat nucleus reticularis pontis oralis (NRPO), antagonized by amantadine, which also increased 5-HT and 5-HIAA levels in the NRPO. It is suggested: a) that the anti-immobility effect of AE37F is related to its antimuscarinic properties, b) that the rate of 5-HT release in the NRPO, calculated here by a new approach (from the 5-HT and 5-HIAA brain levels) is increased by AE37F and decreased by amantadine, in the NRPO, c) that the anti-convulsant action, observed with AE37F, could be related to a NMDA-sigma mediated stimulation of serotoninergic, GABAergic and glycinergic brain neurones, antagonized by the NMDA-sigma inhibition induced by amantadine.Annales Pharmaceutiques Françaises 02/2004; 62(1):49-55.
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ABSTRACT: Intraperitoneal administration of pargyline HCl induced a dose-dependent accumulation of 3-methoxytyramine and normetanephrine in mouse brain in vivo. As judged by the decrease of 5-hydroxyindole acetic acid levels a dose of 200 mg/kg of pargyline appeared to inhibit monoamine oxidase completely. This dose led to an approximately linear accumulation of 3-methoxytyramine and normetanephrine during the first 3 hours. gamma-Butyrolactone, 750 mg/kg i.p. reduced the accumulation of 3-methoxytyramine despite a marked increase of dopamine. (+)-Amphetamine stimulated 3-methoxytyramine as well as normetanephrine accumulation at doses of 3 and 10 mg/kg i.p. In line with the concept of receptor-mediated negative feedback control of catecholaminergic transmission the dopamine receptor agonists apomorphine, 0.3 mg/kg i.p., lisuride, 0.05--0.3 mg/kg i.p., and bromocriptine, 10 mg/kg i.p., decrease 3-methoxytyramine formation while the dopamine receptor blocking agent haloperidol, 1 mg/kg i.p., led to a 3-fold increase. The alpha-adrenoceptor agonist clonidine, 0.1 mg/kg i.p., reduced the formation of normetanephrine and the alpha-adrenoceptor antagonists yohimbine, 10 mg per kg i.p., phenoxybenzamine, 20 mg/kg i.p., and mianserine, 50 mg/kg i.p., stimulated normetanephrine accumulation 1.5- to 4-fold. 3-Methoxytyramine and normetanephrine accumulating after inhibition of monoamine oxidase appear to be reliable indicators of dopamine and noradrenaline release and metabolism.Journal of Neural Transmission 02/1981; 50(2-4):165-78. · 3.05 Impact Factor