Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rilmenidine is an oxazoline derivative with antihypertensive activity which was developed to enhance the dissociation between the hypotensive and adverse effect profile of centrally acting agents. Experimental studies have indicated that rilmenidine is selective for both alpha 2-adrenoceptors (v alpha 1) and newly discovered nonadrenergic imidazoline receptors in the brain and in the periphery. In experimental studies, rilmenidine differs from clonidine in that it is more selective for imidazoline receptors than for alpha 2-adrenoceptors; at equihypotensive doses, rilmenidine causes less bradycardia and reduction in cardiac output, less sedation, and little or no antinociceptive action compared to clonidine. The hypotensive effects of rilmenidine are antagonised by idazoxan and yohimbine, but idazoxan (imidazoline structure) is six times more potent than yohimbine (a selective alpha 2-antagonist). In isolated renal proximal tubule cells, where imidazoline binding has also been shown, rilmenidine inhibits reabsorption of sodium. Clinical studies comparing 1 mg rilmenidine with placebo demonstrated significant reductions in blood pressure (BP) (61% rilmenidine v 23% placebo normalized to 160/90 mm Hg). The reduction in BP was not associated with classical alpha 2 side effects such as dry mouth or daytime drowsiness. Compared with clonidine (0.15 to 0.3 mg), equihypotensive doses of rilmenidine (1 to 2 mg) induced two to three times less dry mouth, daytime drowsiness, and constipation; no orthostatic hypotension was reported. Methyldopa (0.5 to 1 mg) v rilmenidine (1 to 2 mg) indicated a comparable reduction of BP with significantly less weakness, drowsiness, orthostatic dizziness, and dry mouth on rilmenidine; there was no evidence of the "clonidine withdrawal syndrome" on drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Distinctive features of rilmenidine possibly related to its selectivity for imidazoline receptors. 135 Jul 32

Rilmenidine (RIL) is a novel antihypertensive drug selectively acting at the sites of imidazoline receptors. Compared with diuretics, beta-blockers, Ca2+ antagonists and angiotensin converting enzyme inhibitors, the four major groups recommended by the US Joint National Committee as first-line antihypertensive drugs, RIL appears to meet the same criteria of efficacy, safety, and acceptability. Rilmenidine dose-dependently decreases blood pressure (BP), acting as a vasodilator by decreasing vascular resistance through inhibition of the adrenergic nervous system, even while the BP changes due to standing and exercise. In comparison with placebo, RIL significantly decreased BP. In double-blind comparative trials versus first-line diuretics and beta-blockers, RIL normalized BP in approximately 60% patients, showing a similar efficacy to other drugs. In contrast with hydrochlorothiazide, RIL decreased total cholesterol and did not change plasma potassium levels. No tachyphylaxis was observed during long-term treatment. Central side effects, which have contributed to the limitation of the use of alpha 2-agonists as second- or third-line therapy for hypertension, were significantly less frequent with RIL than with clonidine or methyldopa. Indeed, the incidence of dry mouth and drowsiness during double-blind comparative trials versus clonidine and methyldopa was significantly lower with RIL. This absence of central side-effects was confirmed in double-blind comparative trials versus hydrochlorothiazide and atenolol. In contrast with clonidine, no sodium retention or weight gain were observed during chronic treatment with RIL.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Rilmenidine: a novel approach to first-line treatment of hypertension. 135 Jul 33

Acceptability and plasma concentrations of rilmenidine, a new antihypertensive agent mainly eliminated via the kidney, were evaluated in 17 hypertensive patients (supine diastolic blood pressure, 104 +/- 3 mmHg) with renal insufficiency (creatinine clearance, 35 +/- 4 ml.minute-1/1.73 m2; range, 12 to 58). Patients were treated for six months with rilmenidine at the dose of 1 mg in the morning or 1 mg twice daily as single-drug therapy in untreated patients, or in combination or as substitution in patients already treated. Plasma concentrations of rilmenidine were measured by gas chromatography combined with mass spectrometry at Days 0, 1, 5, 7, 9, and 11, and Months 1.5, 3, 4.5, and 6 before administration. Supine and erect blood pressure (sphygmomanometer) measurements and side effects were noted at the same times. Laboratory and electrocardiographic parameters were evaluated at Days 0 and 11, and Months 1.5 and 6. Blood pressure was effectively controlled during the trial in 12 patients (mean decrease in systolic/diastolic blood pressure of 12/8 mmHg). Five patients were removed from the trial after Month 1.5 because of a rise in blood pressure (three cases) or noncompliance (two cases). Side effects were moderate and transient (dry mouth, constipation, daytime drowsiness, mood disturbances, insomnia) never requiring treatment withdrawal. Surveillance of renal function revealed no significant mean variation. Rilmenidine plasma concentrations reached steady state the fifth day at the latest and were related to the degree of renal insufficiency. When renal function was stable (13 cases), plasma concentrations did not vary until the end of the trial. When renal function was progressive (four cases), plasma concentrations increased in parallel in two patients, without the onset of side effects, and remained stable in the other two patients. In conclusion, this study confirmed the good acceptability of rilmenidine in hypertensive patients with chronic renal insufficiency. It showed stable plasma concentrations of rilmenidine during a six-month treatment in hypertensive patients with renal insufficiency, reflecting the absence of accumulation of the drug.
 ...
PMID:Acceptability of rilmenidine and long-term surveillance of plasma concentrations in hypertensive patients with renal insufficiency. 278 26

A double-blind multicenter trial compared rilmenidine with placebo in the treatment of 126 patients with mild to moderate hypertension after a 4-week placebo run-in period. Patients with mild hypertension (study 1) with mean supine diastolic blood pressure (BP) between 95 and 104 mm Hg received either rilmenidine 1 mg/day (n = 31) or placebo (n = 35) for 4 weeks. In study 2, patients with moderate hypertension (mean supine diastolic BP between 105 and 115 mm Hg) received either rilmenidine 1 mg twice a day (n = 30) or placebo twice a day (n = 30) for 4 weeks. All 61 patients taking rilmenidine completed the study; 8 of the 65 patients taking placebo were withdrawn because of an increase in BP. Rilmenidine significantly reduced mean systolic and diastolic BP compared with placebo in both studies. BP was normalized (systolic less than 160 mm Hg and diastolic less than or equal to 90 mm Hg in 61% of the patients taking rilmenidine as opposed to 23% of those taking placebo (p less than 0.001). There was no significant difference in the incidence of either dry mouth or daytime drowsiness between rilmenidine, 1 mg/day, and placebo. Dry mouth was significantly more frequent with rilmenidine, 2 mg/day, than with placebo, but this difference was transient and no longer significant at the end of the study. No unexpected adverse effects occurred. Rilmenidine as single therapy appears to be effective and well accepted in the management of mild to moderate hypertension, in particular at the 1-mg/day dose, which normalized 84% of mild hypertensive patients and did not induce any significant adverse effects compared with placebo.
 ...
PMID:Efficacy and acceptability of rilmenidine for mild to moderate systemic hypertension. 289 64

Centrally acting antihypertensive drugs are recognized to be safe and effective treatment for high blood pressure. Centrally mediated side effects, such as sedation, are commonly dose- and treatment-limiting events. Imidazoline-preferring receptors, while functionally similar to alpha 2 adrenoceptors, are distinguishable not only on the basis of in vitro radioligand binding but also in vivo in terms of side effects. Drugs with an imidazoline structure lower blood pressure but are less likely to impair psychomotor function. A placebo-controlled study compared moxonidine 0.1 mg with clonidine 0.1 mg orally in nine normal subjects. Both active drugs lowered blood pressure compared to placebo (clonidine more than moxonidine). However, psychomotor function and self-scored sedation and dry mouth were significantly affected only by clonidine. In a long-term (4 weeks) double-blind cross-over study in essential hypertension, rilmenidine was well tolerated and had similar effects to those of atenolol on erect and supine blood pressure. Rilmenidine had no effect on a wide range of autonomic and psychomotor tests or on responses to mental or physical stress. Atenolol, by contrast, had the predicted effects of a beta adrenoceptor antagonist on heart rate during exercise and the Valsalva maneuver. Imidazoline-preferring drugs offer a new and realistic approach to antihypertensive therapy with blood pressure reduction not limited by marked sedation within the therapeutic dose range.
 ...
PMID:Clinical pharmacology of drugs acting on imidazoline and adrenergic receptors. Studies with clonidine, moxonidine, rilmenidine, and atenolol. 767 87

It is a fact that sympathetic outflow is a player in most, if not all, hypertensive conditions. A selective, effective, and relatively benign means of controlling it remains high on every clinician's wish list. In this supplement we examine the neurobiologic and pharmacologic evidence that the wish is nearing fulfillment. Recent evidence has documented the existence of nonadrenergic receptors in the brainstem, other than the well-known alpha 2-adrenergic receptors, that bind the imidazoline portion of vasoactive molecules. Pharmacologic science has wasted little time in developing compounds rich in imidazoline-like structures that, by supplanting norepinephrine (the natural cerebral neurotransmitter for sympathetic nervous system outflow) quiet sympathetic outflow, restrain heart rate and vasomotor influence, and reduce the negative quality-of-life effects induced by earlier centrally acting agents. This is because specific ligands for the imidazoline-preferring receptors appear to lower blood pressure without attendant drowsiness, dry mouth, and impaired mentation. Rilmenidine, the subject of this supplement, is the newest such agent, and the scientists involved in its development and clinical trials have produced heartening data. These developments presage good news in the clinic, and I am excited by their potential, particularly that for gaining deeper insight into human pressor phenomena.
 ...
PMID:The high-risk hypertensive patient and the potential for brain imidazoline receptor binding by rilmenidine. 799 83

Rilmenidine is an imidazoline derivative that appears to lower blood pressure (BP) by an interaction with imidazoline (I1) receptors in the brainstem (and kidneys). Rilmenidine is as effective in monotherapy as all other first-line classes of drugs, including diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and calcium antagonists. It is well tolerated and can be taken in combination for greater efficacy. Sedation and dry mouth are not prominent side effects and withdrawal hypertension is not seen when treatment is stopped abruptly. Recently, in addition to a reduction in BP, this agent has been shown to improve glucose tolerance, lipid risk factors, and insulin sensitivity. These changes would be consistent with a reduction in long-term cardiovascular risk, as would recently described actions on the heart (reducing left ventricular hypertrophy) and the kidney (reducing microalbuminuria). Although no data are yet available from prospective long-term outcome studies, rilmenidine could represent an important new development in antihypertensive therapy and the prevention of cardiovascular disease.
 ...
PMID:Update on rilmenidine: clinical benefits. 1172 91