Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacological profile of N,N dipropyl-8-hydroxy-3-chromanamine (DP-8OH-3CA), the oxygen isostere of N,N dipropyl-5-hydroxy-2-aminotetralin (DP-5OH-AT), was studied and the results compared to its carbon analogue and apomorphine. The chromanamine was found to displace the D2-dopaminergic ligand [3H] 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin with a higher potency than apomorphine and DP-5OH-AT; the IC50 values were 8, 11 and 16 nM, respectively. Experiments investigating the effects of these compounds on dopamine metabolism following oral (o.a.) and intraperitoneal administration (i.p.) showed that the chromanamine had an excellent o.a./i.p. ratio. The presynaptic actions on D2-dopamine receptors, which were studied using tyrosine hydroxylase inhibition, modulation of dopamine metabolism, prevention of alpha-methyl-p-tyrosine induced dopamine depletion in rats and hypomotility in mice, showed that the chromanamine acts as a D2-agonist with half maximal effects between 0.1 and 0.4 mumol/kg (i.p.) DP-8OH-3CA was found to evoke obvious postsynaptic effects when studied in such models as stereotyped behaviour, hyperlocomotion, turning behaviour in 6 hydroxydopamine lesioned rats and reserpine reversal. Stereotypy and the accompanying hyperlocomotion were found to be induced at a half maximal dose of 17 mumol/kg (i.p.). Both with the stereotyped and turning behaviours, a long duration of action was evident. The selectivity for presynaptic receptors was found to be 6.7 times higher than that of DP-5OH-AT, indicating that oxygen substitution can cause an enhancement of selectivity for presynaptic D2-dopamine receptors. Experiments on noradrenaline release and on serotonin synthesis showed that DP-8OH-3CA had only moderate affinity for 5-hydroxytryptamine and noradrenaline receptors. It is concluded that DP-8OH-3CA is a potent D2-agonist with an excellent o.a./i.p. ratio and enhanced selectivity for presynaptic dopamine receptors.
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PMID:Pharmacological profile of N,N dipropyl-8-hydroxy-3-chromanamine, an oxygen isostere of the dopamine agonist N,N dipropyl-5-hydroxy-2-aminotetralin with enhanced presynaptic selectivity. 342 84

The ergot derivative pergolide was evaluated as a dopamine agonist using various behavioral and biochemical analyses. Spontaneous motor activity was decreased by small doses (0.1 mg/kg) of pergolide and increased with larger doses (above 0.5 mg/kg). Hypermotility after larger doses persisted for as long as 24 hr and was succeeded by a period of hypomotility. The doses of drug, sufficient to produce hypermotility, also produced stereotypy. With repeated daily injections (2 weeks), the period of hypermotility decreased and the ensuing period of hypomotility increased. Stereotyped behavior was similarly affected. Chronic administration of pergolide did not alter the magnitude of the behavioral responses. Levels of the dopamine (DA) metabolites, dihydroxyphenylacetate (DOPAC) and homovanillic acid (HVA), in the striatum and mesolimbic regions were decreased during the periods of hypermotility but returned to control levels during subsequent hypomotility. Activation of putative inhibitory presynaptic dopamine receptors by pergolide was studied by following accumulation of DOPA in rats treated with the dopamine neuron inhibiting agent, gamma-butyrolactone (GBL) and a DOPA-decarboxylase inhibitor. Pergolide significantly inhibited both striatal and mesolimbic accumulation of DOPA. In contrast, with changes in behavioral and metabolic indices, pergolide-induced inhibition of tyrosine hydroxylase was not affected by chronic treatment with pergolide. On the basis of both behavioral and biochemical data it is proposed that pergolide acts as a dopamine agonist with particularly long-lasting effects.
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PMID:Biochemical and behavioral evaluation of pergolide as a dopamine agonist in the rat brain. 653 28

Dextromethorphan (DM), an antitussive widely available in over-the-counter, has been abused mostly in teenage groups at high doses. To examine effects of DM on the reward pathway, we injected a high dose of DM (40 mg/kg; intraperitoneally) into the adolescent rat and measured tyrosine hydroxylase (TH) mRNA by in situ hybridization in the ventral tegmental area (VTA) and the substantia nigra (SN). Remarkable increases in the level of TH mRNA were observed in the VTA and SN 2 h after DM injection. Stereotyped behavior and ataxia increased, and rearing decreased by DM administration. These results suggest that DM-induced increase in TH mRNA expression in mesencephalon contribute to the reinforcing property and the behavioral effects of DM.
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PMID:Dextromethorphan increases tyrosine hydroxylase mRNA in the mesencephalon of adolescent rats. 1150 51