Rilmenidine selectivity for imidazoline receptors in human brain

“…In addition, we recently observed, through binding tests on human NRL membrane preparations (Bricca et al, 1989b) that rilmenidine, structurally very close to the imidazoline, exhibited a relative selectivity for these receptors. The selectivity of rilmenidine was about 2.5 times higher than that of clonidine for the medullary imidazoline receptors as compared to the cortical a2-adrenoceptors (Bricca et al, 1989b). In the present work we have investigated further the central site of action as well as the hypotensive mechanism of action of rilmenidine in the rabbit.…”

Section: Introductionmentioning

confidence: 96%

Evidence for the involvement of imidazoline receptors in the central hypotensive effect of rilmenidine in the rabbit

Feldman

Tibiriçá

Bricca

et al. 1990

British J Pharmacology

104

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1 Rilmenidine has recently been introduced as a new centrally-acting antihypertensive agent. We examined its cardiovascular effects after intracerebral injection to anaesthetized rabbits. Cumulative doses of rilmenidine injected intracisternally (1 to 300pgkg-1) led to dose-dependent decreases in arterial blood pressure and heart rate. The effective doses of rilmenidine were lower when injected centrally than when injected intravenously. 2 Pretreatment with the same dose of yohimbine or idazoxan shifted the rilmenidine dose-response curves for its hypotensive and bradycardic effects to the right. Idazoxan, which has an imidazoline structure, proved to be a more active antagonist than yohimbine of rilmenidine centrally-mediated cardiovascular effects. 3 The dose-response curve for the central hypotensive effect of rilmenidine was also shifted to the right after pretreatment with a bovine brain extract. This extract contains the endogenous ligand of the imidazoline-preferring receptors which is not a catecholamine. 4 Rilmenidine, like clonidine, proved to be active when micro-injected into the rabbit nucleus reticularis lateralis region. 5In conclusion, rilmenidine exhibited in the rabbit a central hypotensive effect which originated in the same area as where clonidine acts. Specific imidazoline-preferring receptors appear to be involved in this hypotensive effect.

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“…The I, receptor is preferentially labelled by [3H]-clonidine or [3H]-para-aminoclonidine, and the 12 by [3H]-idazoxan. In both man and experimental animals, a high density of I, receptors is found in a specific area of the brainstem, the rostral ventrolateral medullar (RVL; also referred to as the nucleus reticularis lateralis (NRL)) (Ernsberger et al, 1987;Bricca et al, 1989b), and, in the rat, the hypotensive and bradycardiac action of clonidine and other imidazolines, administered via localized microinjection to this region, has been shown to result from activation of I receptors (Ernsberger et al, 1990;Gomez et al, 1991). Thus, the hypotensive action of clonidine could be antagonized by local injection of idazoxan, an antagonist having affinity for both I receptors and C2-adrenoceptors, but not by SK&F 86466 (6-chloro-3-methyl-2,3,4,5-tetrahydro-3-benzazepine) which blocks only the C2-adrenoceptor.…”

Section: Introductionmentioning

confidence: 99%

“…rilmenidine and moxonidine, have been postulated to have greater selectivity than clonidine for I, receptors versus a2-adrenoceptors (Bricca et al, 1989b;Gomez et al, 1992;Ernsberger et al, 1992;. It has been proposed that the relative lack of side effects of these drugs, vis-a-vis clonidine and other clinically used k2-adrenoceptor agonists, results from this selectivity (King et al, 1992;Tibirica et al, 1991b).…”

Section: Introductionmentioning

confidence: 99%

Mediation of the hypotensive action of systemic clonidine in the rat by α₂‐adrenoceptors

Hieble

Kolpak

1993

British J Pharmacology

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1 During the past few years it has been shown that the sympatholytic effect resulting from localized microinjection of clonidine and other imidazolines into the rostral ventrolateral medulla (RVL) results from activation of 'imidazoline' receptors (I, receptors) rather than from an a2-adrenoceptor-mediated effect. 2 The relative contributions of these two receptor systems to the hypotensive action of systemically administered clonidine have not been studied. Clonidine has afffinity for both I1 and a2-adrenoceptors; guanabenz represents a useful pharmacological tool, since it activates only the a2-adrenoceptor. 3 Antagonists acting at both II and M2-adrenoceptors (idazoxan) and at only M2-adrenoceptors (SK&F 86466; 6-chloro-3-methyl-2,3,4,5-tetrahydro-3-benzazepine) are available. Idazoxan (1 mg kg-', i.v.) and SK&F 86466 (3 mg kg-', i.v.) produced an equivalent degree of blockade of the pressor response to guanabenz or clonidine in the pithed rat, a response mediated by the M2-adrenoceptor. 4 Guanabenz (30 gIg kg-', i.v.) and clonidine (10 jig kg-', i.v.) lowered blood pressure in the chloralose-anaesthetized spontaneously hypertensive rat by 48 ± 4.6 mmHg and 44 ± 5.4 mmHg, respectively; this response, for either agonist, was blocked by both idazoxan and SK&F 86466. 5 These data show that the hypotensive effect of intravenously administered clonidine results from activation of central M2-adrenoceptors, with no significant contribution from an 11-mediated effect. Thus clonidine can lower blood pressure by different receptor mechanisms, dependent on the route of administration.

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Rilmenidine selectivity for imidazoline receptors in human brain

Cited by 103 publications

References 8 publications

Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

Evidence for the involvement of imidazoline receptors in the central hypotensive effect of rilmenidine in the rabbit

Mediation of the hypotensive action of systemic clonidine in the rat by α₂‐adrenoceptors

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Rilmenidine selectivity for imidazoline receptors in human brain

Cited by 103 publications

References 8 publications

Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

Evidence for the involvement of imidazoline receptors in the central hypotensive effect of rilmenidine in the rabbit

Mediation of the hypotensive action of systemic clonidine in the rat by α2‐adrenoceptors

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Mediation of the hypotensive action of systemic clonidine in the rat by α₂‐adrenoceptors