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A-Methyl-p-tyrosine

Tyrosine is converted to dopa by the cytoplasmic enzyme tyrosine hydroxylase. This is the rate-limiting step 5 x 10 M) in DA synthesis, it requires molecular O2 and Fe + as well as tetrahydropterine (BH-4) cofactor and is substrate-specific. It can be inhibited by a-methyl-p-tyrosine, which depletes the brain of both DA and NA and it is particularly important for the maintenance of DA synthesis. Since the levels of tyrosine are above the for tyrosine hydroxylase the enzyme is normally saturated and so it is not possible to increase DA levels by giving tyrosine. [Pg.141]

AMPT a-methyl-p-tyrosine CDK cyclin-dependent kinase... [Pg.963]

Appel, J. B., Lovell, R. A., and Freedman, D. X. (1970) Alterations in the behavioral effects of LSD by pretreatment with p-chlorophenylalanine and a-methyl-p-tyrosine. Psychophar-macologia, 18 387-406. [Pg.229]

Other drug effects that decrease DA activity also support this position. Thus, when DA synthesis is blocked by a-methyl- p-tyrosine (AMPT), the dose necessary for an antipsychotic effect is reduced (i.e., the dose-response curve is shifted to the left by the interaction between dopamine and AMPT). A drug such as reserpine that can deplete DA stores also has relatively mild antipsychotic properties. Also, aripiprazole, which has D 2 presynaptic agonist properties, decreases the production of DA, as well as blocking D2 postsynaptic receptors. [Pg.51]

The results with methylphenidate, however, are more impressive. Two of three studies found a significant effect and the third found improvement on the patients subjective evaluation. Although amphetamine and methylphenidate are similar in their pharmacology, they differ in some respects. Amphetamine releases dopamine from newly synthesized pools (a-methyl-p-tyrosine-sensitive pool) whereas methylphenidate releases dopamine from storage sites (reserpine-sensitive sites). This pharmacological difference could be related to the apparent greater efficacy of methylphenidate. [Pg.126]

Rogers DC, Dunnett SB (1989) Hypersensitivity to a-methyl-p-tyrosine suggests that behavioural recovery of rats receiving neonatal 6-OHDA lesions is mediated by residual catecholamine neurons. Neurosci Lett 702 108-113. [Pg.295]

Buydens P, Govaerts J, Velkeniers B, Finne, Vanhaelst L (1988) The effect of bombesin on basal, a-methyl-p-tyrosine, haloperidol, morphine, bremazocine and stress-induced prolactin secretion. Life Sci 43 1755-1760. [Pg.500]

Eden S, Bolle P, Modigh K (1979) Monoaminergic control of episodic growth hormone secretion in the rat effects of reserpine, a-methyl-p-tyrosine, p-chlorophenylalanine, and halperidol. Endocrinology 105 523-529. [Pg.504]

The sedative effect of palmatine on locomotor activity and concentration of monoamine in rats was studied via behavioral and biochemical methods. Palmatine was shown to enhance the hypomotility induced by a-methyl-p-tyrosine, reserpine, and 5-hydroxytryptophan, but reduced the hypermotility produced by L-dopa plus benserazide and p-chlorophenylalanine. In addition, the alkaloid significantly decreased the concentration of dopamine and homovanillic acid in the cortex and the concentration of serotonin in the brain stem, but increased the concentration of 5-HT in the cortex and 5-hydroxyindole acetic acid in the brain stem. These results suggest that the sedative action associated with palmatine may be related to the decrease in catecholamine concentration in the cortex and serotonin in the brain stem, and the increase in the concentration of 5-HT in the cortex [309],... [Pg.159]

The most recent evidence suggests that the false transmitter hypothesis might, after all, furnish the better explanation of the mode of action of a-MMT. a-Methyl [p) tyrosine (a-MT) causes a loss of noradrenaline from the brain and, unlike a-MMT, it produces sedation in a number of animal species. a-MT also inhibits the conditioned avoidance response and this inhibition is correlated, to some extent at least, with a reduction in the noradrenaline content of the brain . It is also clear that the sympathomimetic activities of metaraminol and a-methylnoradrenaline are not so uniformly less than that of noradrenaline as was at first thought the relative potencies of these compounds depend very much on the species and preparation studied. There is also recent evidence that the replacement of noradrenaline by the false transmitters is accompanied by an increased sensitivity of the effector organs . It should, perhaps, be added that these facts, though welcome to the neuropharmacologist, make it even more difficult to explain the efficacy of a-methyldopa as a hypotensive agent. [Pg.299]

Piribedil ( ), a dopamine agonist, suppresses food intake in rats and this effect is not antagonized by a-methyl-p-tyrosine, metergoline, propranolol, phentolamine or domperidone but is blocked by pimozide. Motor activity is increased at 2 to 3 times the doses needed for food intake suppression. [Pg.159]

Brogden RN, Heel RC, Speight TM, etal. a-Methyl-p-tyrosIne a review of Its pharmacology and clinical use. Drugs 1981 21(2) 81-89. [Pg.593]

To study DA turnover, BC-PL were injected into mice pretreated with a-methyl-p-tyrosine (a-MT) (Fig. 2). a-MT induces catecholamine disappearance by means of an inhibitory effect on tyrosine hydroxylase activity (Anden et al, 1972 NybUch Sedwall, 1968). Immediately after the injection, BC-PL potentiate the disappearance of DA, whereas after a certain period of time, they reverse the a-MT effect. The first effect is interpreted as an increased release, neuroleptics behave in the same manner (NybSch Sedwall, 1968), while the second effect may be interpreted in terms of an increased synthesis. [Pg.409]

Fig. 2. Effect of BC-PL (100 mg/kg i.v.) on cerebral DA in mice pretreated with a-methyl p-tyrosine ( a-MT 200 mg/kg i.p.). Values... Fig. 2. Effect of BC-PL (100 mg/kg i.v.) on cerebral DA in mice pretreated with a-methyl p-tyrosine ( a-MT 200 mg/kg i.p.). Values...
Synonyms a-Methyltyrosine a-methyl-p-tyrosine a methyl-L-tyrosine ... [Pg.743]

A new technique to assess changes in NE synthesis in rat brain measures the accumulation of 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG), a major NE metabolite.80 This method was claimed to be more convenient than conventional methods utilizing exogeneous a-methyl-p-tyrosine or labeled tyrosine, and to avoid errors that might be... [Pg.7]

Other approaches to this problem of amine turnover as applied to catecholamines in brain have been to follow either (a) the rate of disappearance of endogenous NE after inhibition of catecholamine biosynthesis by a-methyl-p-tyrosine or (b) the rate of disappearance of synthesized... [Pg.273]


See other pages where A-Methyl-p-tyrosine is mentioned: [Pg.57]    [Pg.161]    [Pg.478]    [Pg.212]    [Pg.891]    [Pg.27]    [Pg.207]    [Pg.30]    [Pg.187]    [Pg.322]    [Pg.126]    [Pg.128]    [Pg.649]    [Pg.118]    [Pg.131]    [Pg.135]    [Pg.969]    [Pg.158]    [Pg.278]    [Pg.228]    [Pg.235]    [Pg.262]    [Pg.262]    [Pg.26]    [Pg.246]    [Pg.183]    [Pg.180]    [Pg.184]    [Pg.190]   
See also in sourсe #XX -- [ Pg.29 ]

See also in sourсe #XX -- [ Pg.223 , Pg.237 , Pg.239 , Pg.248 , Pg.252 , Pg.257 , Pg.258 , Pg.265 , Pg.322 , Pg.447 , Pg.448 , Pg.465 , Pg.466 , Pg.478 ]

See also in sourсe #XX -- [ Pg.270 , Pg.299 ]

See also in sourсe #XX -- [ Pg.182 ]




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