2011
DOI: 10.1111/j.1755-5922.2011.00269.x
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Imidazoline Antihypertensive Drugs: Selective I1‐Imidazoline Receptors Activation

Abstract: SUMMARYInvolvement of imidazoline receptors (IR) in the regulation of vasomotor tone as well as in the mechanism of action of some centrally acting antihypertensives has received tremendous attention. To date, pharmacological studies have allowed the characterization of three main imidazoline receptor classes, the I 1 -imidazoline receptor which is involved in central inhibition of sympathetic tone to lower blood pressure, the I 2 -imidazoline receptor which is an allosteric binding site of monoamine oxidase B… Show more

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Cited by 36 publications
(31 citation statements)
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“…I1R in the rostral ventrolateral medulla of the brainstem, which are stimulated by moxonidine [8][9][10], is reported to inhibit oxidative stress [22]. Moreover, chronic ICV infusion of moxonidine at this dosage enhances endogenous nitric oxide andg-aminobutyric acid release, which interact with brain oxidative stress in the rostral ventrolateral medulla [19,20].…”
Section: Discussionmentioning
confidence: 96%
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“…I1R in the rostral ventrolateral medulla of the brainstem, which are stimulated by moxonidine [8][9][10], is reported to inhibit oxidative stress [22]. Moreover, chronic ICV infusion of moxonidine at this dosage enhances endogenous nitric oxide andg-aminobutyric acid release, which interact with brain oxidative stress in the rostral ventrolateral medulla [19,20].…”
Section: Discussionmentioning
confidence: 96%
“…The lower end (shorter arm) of the cannula (Alzetbrain infusion kit 2; DURECT Corporation, Cupertino, California, USA) was placed at a depth of 3.5 mm from the dura, and the upper end (longer arm) was connected to an osmotic minipump (Alzet Model 2006; DURECT Corporation) for chronic ICV infusion of moxonidine (4 mmol/l; infusion rate 0.15 ml/h for 42 days) or vehicle [artificial cerebrospinal fluid (aCSF) pH 7.4] as a control at 0.15 ml/h for 42 days. This approach was used to observe the direct central sympathoinhibitory effect of a much smaller dose of moxonidine to exclude potential peripheral actions of moxonidine, such as on the kidney and heart [10,21,22]. Moxonidine was obtained from Sigma Aldrich Corporation (St Louis, Missouri, USA) and dissolved in aCSF.…”
Section: Intracerebroventricular Cannulation and Infusion Of Moxonidinementioning
confidence: 99%
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“…The binding sites for these drugs have not been identified definitively, but three IR subtypes (I 1 -, I 2 - and I 3 -Rs) have been distinguished pharmacologically (Eglen et al 1998; Head and Mayorov 2006). I 1 Rs are found in highest density in the brainstem, primarily in RVLM and CVLM (Moreira et al 2004), are localized to plasma membranes, are principally neuronal, and have high affinity for the anti-hypertensive drugs containing a synthetic imidazoline ring (Bousquet et al 1984; Ernsberger et al 1990; De Vos et al 1994; Ernsberger and Haxhiu 1997; Wang et al 2003; Chan et al 2005; Nikolic and Agbaba 2012). In addition, several studies have suggested that I 1 Rs are coupled to G-protein-mediated signal transduction pathways, resulting in the activation of phosphatidylcholine-sensitive phospholipase C (Separovic et al 1997), increased phosphorylation of mitogen-activated protein kinases (MAPK1 and MAPK3) (Zhang and Abdel-Rahman 2005), and inhibition of adenylate cyclase (Greney et al 2000).…”
Section: Discussionmentioning
confidence: 99%