Central and peripheral cardiovascular effects of alpha-methylepinephrine.
Abstract
We compared peripheral and central cardiovascular effects of (+/-)-alpha-methylepinephrine (alpha-ME) and (+/-)-alpha-methylnorepinephrine (alpha-MNE), two putative active metabolites of alpha-methyldopa to those of (-)-epinephrine in urethane-anesthetized normotensive rats. Intravenous administration of 1 microgram doses of alpha-ME (4.3 nmol) lowered blood pressure whereas alpha-MNE (4.5 nmol) and (-)-epinephrine (3.0 nmol) raised blood pressure. Heart rate responses to each were opposite to the blood pressure response, consistent with reflex buffering. When administered into the cerebral ventricle (5-20 micrograms) (15-90 nmol) and nucleus of the solitary tract (0.3-10 nmol), each catecholamine caused marked reductions in both blood pressure and heart rate. alpha-ME was more potent than alpha-MNE and the endogenous catecholamine, (-)-epinephrine, in its central depressor effect. The greater potency of alpha-ME relative to alpha-MNE and (-)-epinephrine suggests that it could contribute to antihypertensive actions of alpha-methyldopa.
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Norepinephrine released in the brain can either increase or decrease sympathetic outflow.
“Norepinephrine released in the brain can either increase 30,31 or decrease 32 sympathetic outflow.”
From Orthostatic Intolerance and Tachycardia Associated with Norepinephrine-Transporter Deficiency (2000) · cites this paper as [31]
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Orthostatic Intolerance and Tachycardia Associated with Norepinephrine-Transporter Deficiency
Shannon, J. R., Flattem, N. L., Jordan, J., Jacob, G., Black, B. K., Biaggioni, I., Blakely, R. D., & Robertson, D. (2000) · New England Journal of Medicine · doi:10.1056/nejm200002243420803 · Cited by 594 · see citing works
Self-citationFamilial orthostatic tachycardia due to norepinephrine transporter deficiency
ROBERTSON, D., FLATTEM, N., TELLIOGLU, T., CARSON, R., GARLAND, E., SHANNON, J. R., JORDAN, J., JACOB, G., BLAKELY, R. D., & BIAGGIONI, I. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb03703.x · Cited by 64 · see citing works
Self-citationThe broader view: catecholamine abnormalities.
Vincent, S., & Robertson, D. (2002) · Clinical Autonomic Research · doi:10.1007/s102860200018 · Cited by 24 · see citing works
Self-citationBoth α- and β-adrenoceptors contribute to the central depressor effect of catecholamines
Tung, C., Goldberg, M. R., Hollister, A. S., & Robertson, D. (1988) · Brain Research · doi:10.1016/0006-8993(88)90347-2 · Cited by 16 · see citing works
Self-citationCarson, R. P., Diedrich, A., & Robertson, D. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00033.2002 · Cited by 15 · see citing works
Self-citationAdrenaline in the CNS and the action of antihypertensive drugs
Ward-Routledge, C., & Marsden, C. A. (1988) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(88)90087-9 · Cited by 14 · see citing works
Antihypertensive metabolites of alpha-methyldopa.
Robertson, D., Tung, C., Goldberg, M. R., Hollister, A. S., Gerkens, J. F., & Oates, J. A. (1984) · Hypertension · doi:10.1161/01.hyp.6.5_pt_2.ii45 · Cited by 11 · see citing works
Self-citationCostall, B., Gunning, S. J., Naylor, R. J., & Tattersall, F. D. (1986) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1986.tb04500.x · Cited by 5 · see citing works
Langham, M. E. (1984) · Experimental Eye Research · doi:10.1016/0014-4835(84)90077-0 · Cited by 4 · see citing works
Beltrutti, D. P. C., Moessinger, S., & Varrassi, G. (2000) · Current Review of Pain · doi:10.1007/s11916-000-0013-7 · Cited by 4 · see citing works
Alpha-Methyladrenaline: A Possible Active Metabolite of Alpha-Methyldopa in the Rat Brain
Himeno, A., Kunisada, K., Niwa, M., & Ozaki, M. (1985) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.39.91 · Cited by 2 · see citing works
Correlation between fall in blood pressure and in vivo amine release after α-methylDOPA
Kapoor, V., & Chalmers, J. P. (1989) · European Journal of Pharmacology · doi:10.1016/0014-2999(89)90261-6 · Cited by 2 · see citing works
Tung, C., Goldberg, M. R., Hollister, A. S., Sweetman, B. J., & Robertson, D. (1988) · Life Sciences · doi:10.1016/0024-3205(88)90190-7 · Cited by 2 · see citing works
Self-citationTung, C., Chen, S.-Z., Hsu, C.-H., & Tseng, C. (1989) · Clinical and Experimental Hypertension · doi:10.3109/10641968909035290 · Cited by 1 · see citing works
Self-citation
- Authors
- Tung, C. S., Goldberg, M. R., Hollister, A. S., Oates, J. A., & Robertson, D.
- ORCID
- Tung, C S
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1983-11
- Volume
- 227
- Issue
- 2
- Pages
- 484-490
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1920396146
- Cited by
- 14
- References
- 0
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institutes of Health (5k04gm000494-05)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- alpha-methylnorepinephrine, epinephrine, central cardiovascular effects, blood pressure, heart rate, nucleus tractus solitarius, antihypertensive mechanism
- MeSH terms
- Animals, Blood Pressure, Epinephrine, Heart Rate, Male, Methyldopa, Nordefrin, Rats, Inbred Strains, Rats
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