Antihypertensive metabolites of alpha-methyldopa.

alpha-Methyldopa acts through a metabolite in the central nervous system. Of the three metabolites most prominently considered as potential mediators of alpha-methyldopa hypotension--alpha-methyldopamine, alpha-methylnorepinephrine (MNE), and alpha-methylepinephrine (ME)--ME is the most potent depressor agent following intravenous infusion into rats, following injection into the lateral ventricle, and following injection into the solitary tract nucleus (NTS). The depressor effect of ME in the NTS is attenuated as effectively by timolol as by yohimbine, while the combination of both timolol and yohimbine completely abolishes the pharmacological activity of ME in the NTS. ME is approximately eightfold more potent than MNE in the NTS and also has a greater susceptibility to timolol attenuation.

[1]  P. Waldmeier,et al.  On the role of α-methyldopamine in the antihypertensive effect of α-methyldopa , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[2]  A. Heise,et al.  Central nervous α-adrenergic receptors and the mode of action of α-methyldopa , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[3]  E. Muscholl.  Biosynthese (aus α-Methyldopa), Aufnahme und Freisetzung von α-Methyladrenalin , 2004, Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie.

[4]  D. Reis,et al.  Brain stem catecholamine mechanisms in tonic and reflex control of blood pressure. , 1984, Hypertension.

[5]  J. Oates,et al.  Central and peripheral cardiovascular effects of alpha-methylepinephrine. , 1983, The Journal of pharmacology and experimental therapeutics.

[6]  M. Goldberg,et al.  Hypertensive effect of yohimbine following selective injection into the nucleus tractus solitarii of normotensive rats , 1983, Brain Research.

[7]  M. Goldberg,et al.  Yohimbine: a pharmacological probe for study of the alpha 2-adrenoreceptor. , 1983, Pharmacological reviews.

[8]  P. Beart,et al.  α‐Methyladrenaline is a central metabolite of α‐methyldopa , 1983 .

[9]  J. Egle,et al.  Adrenergic receptors in the nucleus tractus solitarii of the rat. , 1982, European journal of pharmacology.

[10]  M. Goldberg,et al.  (αS)-ERYTHRO-α-METHYLEPINEPHRINE: PREPARATION AND STEREOSELECTIVE BINDING TO ADRENERGIC RECEPTORS IN RAT FOREBRAIN , 1982 .

[11]  J. Oates,et al.  Differential competition by L-alpha-methyldopa metabolites for adrenergic receptors in rat forebrain. , 1982, The Journal of pharmacology and experimental therapeutics.

[12]  M. Goldberg,et al.  (alpha S)-erythro-alpha-methylepinephrine: preparation and stereoselective binding to adrenergic receptors in rat forebrain. , 1981, Journal of medicinal chemistry.

[13]  R. Murphy,et al.  Hypotension and hypothalamic amine metabolism after long-term α-methyldopa infusions , 1978 .

[14]  W. Pettinger,et al.  A functional basis for classification of α-adrenergic receptors , 1977 .

[15]  F. Nijkamp,et al.  Centrally Induced Hypotension by α-Methyldopa and α-Methylnoradrenaline in Normotensive and Renal Hypertensive Rats , 1977 .

[16]  S. Koslow,et al.  Quantitation of adrenaline in rat brain nuclei and areas by mass fragmentography , 1974, Nature.

[17]  T. Hökfelt,et al.  Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. , 1974, European journal of pharmacology.

[18]  K. Fuxe,et al.  Immunohistochemical evidence for the existence of adrenaline neurons in the rat brain , 1974 .

[19]  T. Hökfelt,et al.  Evidence for adrenaline neurons in the rat brain. , 1973, Acta physiologica Scandinavica.

[20]  K. Malik.  Effect of (±) dihydroxy ephedrine and (±) dihydroxy pseudoephedrine on adrenergic transmission in mesenteric arteries , 1971 .

[21]  R. Connett,et al.  Purification and properties of bovine phenylethanolamine N-methyltransferase. , 1970, The Journal of biological chemistry.

[22]  E. Muscholl.  RELEASE OF CATECHOLAMINES FROM THE HEART , 1966 .

[23]  J. M. Hunt,et al.  Substrate specificity of phenethanolamine N-methyl transferase. , 1965, Biochemical pharmacology.

[24]  F. Pohl.  Zur Schnellbestimmung von Metallspuren in Reaktorwässern , 1963 .

[25]  J. Axelrod.  Purification and properties of phenylethanolamine-N-methyl transferase. , 1962, The Journal of biological chemistry.

[26]  R. Ahlquist,et al.  A study of the adrenotropic receptors. , 1948, The American journal of physiology.