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[Alpha-methyldopa and brain monoamines].
- Source :
-
Nihon yakurigaku zasshi. Folia pharmacologica Japonica [Nihon Yakurigaku Zasshi] 1982 May; Vol. 79 (5), pp. 451-9. - Publication Year :
- 1982
-
Abstract
- Alpha-methyldopa (alpha-MDP) is a widely used hypotensive agent, and it is considered to act on the central nervous system. In the present study, 6-hydroxydopa (6-OHDP) was injected into spontaneously hypertensive rats in a dose of 50 mg/kg on the 19th and 21st days of gestation. Dopamine contents were not changed, but norepinephrine (NE) decreased at 12 weeks of age. When the effect of alpha-MDP was examined at the age of 30 to 40 weeks, the decrease in blood pressure induced by 300 mg/kg alpha-MDP i.p. was significantly attenuated in the 6-OHDP treated rats. Whenever the hypotensive effects of alpha-MDP were inhibited, production of alpha-methylnorepinephrine (alpha-MNE) was markedly reduced only in the spinal cord. 6-Hydroxydopamine (6-OHDA) was also injected into the spinal cord at the C4 level. Although alpha-MDP lowered blood pressure in both 6-OHDA treated and non-treated control rats, the decreased in 6-OHDA treated rats tended to be less pronounced. The accumulation of alpha-MNE in the caudal area of the spinal cord was markedly reduced. Furthermore, in order to destroy the spinal serotonergic neurons selectively, we used intraspinal 5,7-dihydroxytryptamine (5,7-DHT) in the same manner as 6-OHDA injection. In 5,7-DHT treated rats, the blood pressure was decreased fully. These observations seem sufficient to hypothesize, although not to conclude, that the effect of alpha-MDP on the blood pressure is dependent at least partly on the biotransformation to alpha-MNE in the spinal noradrenergic neurons.
- Subjects :
- Animals
Biotransformation
Dihydroxyphenylalanine analogs & derivatives
Dihydroxyphenylalanine pharmacology
Female
Gestational Age
Hypertension drug therapy
Male
Methyldopa metabolism
Neurons metabolism
Nordefrin metabolism
Pregnancy
Rats
Rats, Inbred Strains
Spinal Cord metabolism
Sympathectomy, Chemical
Antihypertensive Agents
Brain metabolism
Catecholamines metabolism
Methyldopa pharmacology
Subjects
Details
- Language :
- Japanese
- ISSN :
- 0015-5691
- Volume :
- 79
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nihon yakurigaku zasshi. Folia pharmacologica Japonica
- Publication Type :
- Academic Journal
- Accession number :
- 6813206