Central monoamine systems and new antihypertensive agents.
This review describes the relationship between central monoamine pathways and centrally acting antihypertensive agents. By using antagonists with affinity for alpha 2-adrenoceptors and also imidazoline receptors we have found that the first generation agents clonidine and alpha-methyldopa activate alpha 2-adrenoceptors while the newer second generation antihypertensive agents rilmenidine and moxonidine activate imidazoline receptors. Despite the difference in receptors activated, the hypotension produced by central administration of all agents was attenuated after chemical lesioning of the brainstem noradrenergic or serotonergic pathways suggesting a similar dependence on central monoamine pathways. Since the acute 6-hydroxydopamine-induced release of noradrenaline in the brainstem produces hypotension it suggests that these agents normally mimic brainstem noradrenergic function. By contrast the pressor response shortly following 5,6-dihydroxytryptamine suggests serotonergic neurones in the brainstem are pressor and that part of the anti-hypertensive action of centrally acting antihypertensive agents is mediated by inhibition of bulbar serotonergic pathways. We suggest that the similar haemodynamic and baroreflex effects of the two generations of agents can be explained by the alpha 2-adrenoceptors and the imidazoline receptors being in series along the noradrenergic and serotonergic pathways.
Head
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GA
Neuropharmacology Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D015306:Biogenic Monoamines / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D054755:Imidazoline Receptors; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology
D000959:Antihypertensive Agents; D015306:Biogenic Monoamines; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D012701:Serotonin; D009638:Norepinephrine