Disease relevance of Racemetirosine

• Reduction in the size of a pheochromocytoma pulmonary metastasis by metyrosine therapy [1].
• Therapy with the catecholamine synthesis inhibitor metyrosine (alpha-methyltyrosine) reversed the catecholamine excess but had no effect on the hypercalcemia [2].
• Surgical management of pheochromocytoma with the use of metyrosine [3].
• To assess the hemodynamic contribution of circulating catecholamines, metyrosine (alpha-methyl-p-tyrosine), an inhibitor of catecholamine synthesis, was administered to nine patients with acutely decompensated chronic congestive heart failure [4].
• Special toxicity is discussed with reference to methyldopa, clonidine, monoamine oxidase inhibitors, and metyrosine [5].

Psychiatry related information on Racemetirosine

• The compounds were evaluated using a battery of three murine bioassays, including stimulation of locomotor activity, induction of circling in animals with unilateral striatal lesions, and reversal of reserpine/alpha-methyltyrosine induced akinesia [6].
• Circadian variations in the effect of alpha-methyl-p-tyrosine on avoidance learning [7].
• Treatments that increased intracellular cyclic 3',5' adenosine monophosphate (cAMP) levels following catecholamine depletion caused by alpha-methyl-p-tyrosine (AMPT) provided a prophylactic effect against AMPT-induced amnesia [8].
• Reserpine did not inhibit the apomorphine-induced stereotyped behavior though the drug elicited markedly the behavioral depression and alpha-methyl-p-tyrosine also did not block the stereotyped behavior [9].
• Injection of reserpine followed by alpha-methyl-p-tyrosine virtually eliminated self-stimulation [10].

High impact information on Racemetirosine

• Increases in plasma prolactin concentrations produced by alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, varied inversely with baseline platelet monoamine oxidase activity in 12 patients with chronic schizophrenia [11].
• Treatment of the mussel Mytilus edulis with 6-hydroxydopamine or with alpha-methyl-p-tyrosine decreased dopamine and increased serotonin in the nervous system [12].
• Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA [13].
• A similar increase in GSH content was observed after depletion of DA stores with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine [14].
• To determine the effect of catecholamine depletion on ocular motor pathways in humans, we studied the eye movements of 3 normal subjects who received the drug metyrosine (alpha-methylparatyrosine) [15].

Chemical compound and disease context of Racemetirosine

• Sudden onset of a hypertensive crisis occurred shortly after induction of anesthesia in a patient with malignant pheochromocytoma, despite preoperative medical preparation with alpha-methyltyrosine (alpha-methyl-p-tyrosine) and propranolol hydrochloride [16].
• Using enzyme purified from a rat pheochromocytoma, we found that tyrosine, alpha-methyl-p-tyrosine, and a 3-iodotyrosine protected the phosphorylated enzyme against the inactivation produced by tetrahydrobiopterin [17].
• A high dose (80 micrograms) of dopamine increased the motor activity of normal as well as alpha-methyltyrosine- and reserpine-treated rats [18].
• The inhibitor of catecholamine synthesis alpha-methyl-p-tyrosine, the alpha-adrenergic blocker phentolamine and the muscarinic antagonist atropine failed to alter the hypothermia [19].
• Apomorphine, a dopamine (DA) agonist, and biperiden, an acetylcholine (ACh) antagonist, decreased acute dystonia, whereas alpha-methyl-p-tyrosine (AMPT), an inhibitor of DA synthesis, and physostigmine, an ACh agonist, agonist, increased the symptoms [20].

Biological context of Racemetirosine

• Saccadic, pursuit, and vestibulo-ocular eye movements were recorded using infrared oculography with subjects both on placebo and on metyrosine [15].
• There were no significant differences in maximum, minimum, or mean blood pressure before or after tumor resection between patients who received metyrosine and those who did not [3].
• We administered the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (AMPT) to five women in the early follicular phase (one of menstrual cycle days 2-5) of the menstrual cycle and compared TSH secretion patterns to those in five women at the same time in the cycle who did not receive AMPT [21].
• We administered the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT, 500 mg at 800 and 1000 h) to five women in the early follicular phase of the menstrual cycle and compared LH secretion patterns to those in five untreated controls [22].
• While apoptosis due to overexpression of WT alpha-syn was completely abrogated by a specific tyrosine hydroxylase (TH) inhibitor, alpha-methyl-p-tyrosine (alpha-MT), the inhibitor only partially rescued apoptosis caused by overexpression of alpha-syn mutants [23].

Anatomical context of Racemetirosine

• Ang II (100 ng) or saline (vehicle control) was administered into the cerebral ventricle 30 minutes after injection of alpha-methyl-p-tyrosine (250 mg/kg IP) [24].
• Sympathetic nervous system activity was assessed by tissue norepinephrine turnover, which was determined from the rate of decline of tissue norepinephrine concentration after the administration of alpha-methyl-p-tyrosine, a potent inhibitor of the rate-limiting step of catecholamine synthesis [25].
• Changes in noradrenergic activity were assessed by measuring norepinephrine (NE) levels in the hypothalamus, frontal cortex, and hippocampus following inhibition of NE synthesis with alpha-methyl-p-tyrosine (alpha-MpT) (300 mg/kg, i.p., 2 h) [26].
• None of the nine units sampled from rats pre-treated with alpha-methyl-p-tyrosine injected twice I.P. (250 mg/kg for each) were facilitated by stimulation of the median eminence following I.V. picrotoxin, while eight of the eleven units sampled from control rats pre-treated with L-tyrosine could be facilitated by antidromic stimulation [27].
• The effects of a 4-day administration of two sympathicolytic (alpha-methyl-p-tyrosine, propranolol) and three sympathicomimetic (clorgyline, isoproterenol, dobutamine) drugs on the ultrastructure of the pineal gland in the domestic pig were examined [28].

Associations of Racemetirosine with other chemical compounds

• Both 3-iodotyrosine and alpha-methyl-p-tyrosine competitively inhibited the recombinantly produced tyrosine hydroxylase with Ki values of 1.2 and 16 microM, respectively, similar to those previously reported for the rat and human enzymes [29].
• Study of selected patients matched for age and severity of disease suggested that the intraoperative blood pressure management of patients prepared with phenoxybenzamine and metyrosine was facilitated [3].
• In addition, the levels of dopamine, 5-HT, octopamine, alpha-methyl-p-tyrosine, and tryptophan were determined after injection of alpha-methyl-p-tyrosine, 6-hydroxydopamine, or 5,7-dihydroxytryptamine directly into the cerebral ganglia by means of microinjection needles [30].
• Haloperidol (2.5 mg/kg BW) caused a 90% increase in serum PRL concentrations in diestrous rats 1 h after sc injection. alpha-Methyl-p-tyrosine (200 mg/kg BW, ip) stimulated in vivo PRL secretion, monitored 1, 4, and 24 h after drug administration [31].
• Administration of alpha-methyl-p-tyrosine (AMT) methyl ester HCl (100 mg/kg) had no effect on the activity of tryptophan hydroxylase, but effectively eliminated the peak of tyrosine hydroxylase activity that occurred during the light phase [32].

Gene context of Racemetirosine

• Furthermore, icv CCK-8 increased plasma PRL levels in rats depleted of dopamine by pretreatment with reserpine and alpha-methyl-p-tyrosine [33].
• Injection of alpha-methyl-p-tyrosine (alpha-MT; 50 mg/kg), an inhibitor of dopamine synthesis, increased PRL levels, and suckling caused a further increase in the plasma concentrations of PRL [34].
• 0.1 microgram/kg X min DA infusion fully normalized PRL serum levels in 8 normal cycling women whose endogenous catecholamine synthesis had been inhibited by alpha-methyl-p-tyrosine (AMPT) pretreatment [35].
• We have previously shown that pharmacological inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine results in a dose-related inhibition of locomotor activity in adult organisms [36].
• Other groups of rats were injected intraperitoneally with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, or with the inhibitor of dopamine-beta-hydroxylase, FLA-63 [37].

Analytical, diagnostic and therapeutic context of Racemetirosine

• This treatment period was terminated by a double-blind crossover design, and the activity of metyrosine was corroborated in all cases [38].
• Whereas acute DA depletion [produced by the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT)] attenuated the inhibitory effects of quinpirole on CPu neurons, long-term DA denervation (produced by 6-OHDA) enhanced the inhibitory effects of the D2 agonist [39].
• There were significant differences between the mean TSH concentrations in the AMPT-treated (2.51 +/- 0.09 mIU/L) vs. the control group (1.28 +/- 0.09 mIU/L; P < 0.0001) for the entire study [21].
• Two days later, the PVN was perfused continuously with Ringer's solution or Ringer's solution containing a catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine (100 microM), through a microdialysis probe inserted in the guide cannula 2 h before the beginning of sampling, which lasted 3 h [40].
• Narrow cisterns of this form of endoplasmic reticulum and lamellar whorls were observed after treatment with alpha-methyl-p-tyrosine in pinealocytes with large dense bodies [28].

References