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20-September-2008 09:55:49 - Moxonidine Moxonidine Systematic IUPAC name 4-chloro-N-4,5-dihydro-1H-imidazol-2-yl- 6-methoxy-2-methylpyrimidin-5-amine Identifiers CAS number 75438-57-2 ATC code C02AC05 PubChem 4810 Chemical data Formula C9H12ClN5O Mol. mass 241.677 g/mol Pharmacokinetic data Bioavailability 88% Metabolism ? Half life 2.2 hours Excretion Renal Therapeutic considerations Pregnancy cat. B3AU Legal status POMUK Routes Oral Moxonidine INN pronounced /mÉ’kˈsÉ’nɪdiË?n/ is a new generation centrally acting antihypertensive drug licensed for the treatment of mild to moderate essential hypertension. It may have a role when thiazides, beta-blockers, ACE inhibitors and calcium channel blockers are not appropriate or have failed to control blood pressure. In addition, it demonstrates favourable effects on parameters of the insulin resistance syndrome, apparently independent of blood pressure reduction. It is manufactured by Solvay Pharmaceuticals under the brand name Physiotens. Contents 1 Mechanism of actions 2 Pharmacodynamic properties 3 Safety pharmacology 4 Cautions 5 Drug interactions 6 Contra-indications 7 Side-effects 8 References Mechanism of actions Moxonidine is a selective agonist at the imidazoline receptor subtype 1 I1. This receptor subtype is found in both the rostral ventro-lateral pressor and ventromedial depressor areas of the medulla oblongata. Moxonidine therefore causes a decrease in sympathetic nervous system activity and, therefore, a decrease in blood pressure. Compared to the older central-acting antihypertensives, moxonidine binds with much greater affinity to the imidazoline I1-receptor than to the α2-receptor. In contrast, clonidine binds to both receptors with equal affinity. In addition, moxonidine may also promote sodium excretion, improve insulin resistance and glucose tolerance and protect against hypertensive target organ damage, such as kidney disease and cardiac hypertrophy. Pharmacodynamic properties Effects on insulin resistance In all animal models of insulin resistance, moxonidine had striking effects on the development of insulin resistance, hyperinsulinaemia and impaired glucose homeostasis. Given the importance of insulin resistance as a risk factor for cardiovascular disease, it is of considerable relevance that it has been shown to improve insulin sensitivity. Based on animal models, it has demonstrated that moxonidine is capable of: normalising plasma insulin levels improving glucose uptake in peripheral cells lowering lipid levels decreasing food intake and reducing weight gain in obese animals. Renal function Evidence is accumulating to show that sympathetic overactivity is substantially involved in the development and progression of chronic renal failure, contributing to a poor overall cardiovascular prognosis. Moxonidine has been shown to reduce structural renal damage in various models of renal failure. Cardiac structure In spontaneously hypertensive rats, moxonidine significantly reduced total heart weight, left ventricular weight and the ratio of ventricular weight to body weight compared with an untreated control group. Safety pharmacology Routine toxicology studies have provided no evidence that moxonidine has any teratogenic, mutagenic or carcinogenic potential. No evidence has been found of serious adverse effects on organs or organ systems, and the drug has not been shown to have deleterious effects on perinatal or postnatal growth and development. Cautions Moxonidine should be avoided in patients with moderate to severe renal impairment. Abrupt discontinuation of the drug should also be avoided. If concomitant treatment with a beta blocker has to be stopped, the beta blocker should be discontinued first, then moxonidine after a few days. Drug interactions Concomitant administration of moxonidine and a thiazide diuretic such as hydrochlorothiazide is not indicated, as both drugs' hypotensive effects may be enhanced. Contra-indications It is contraindicated if there has been a past history of angioedema; heart conduction disorders e.g. sick sinus syndrome, second- or third-degree heart block; bradycardia; severe heart failure or coronary artery disease, severe liver or renal impairment. Also: Raynaud's syndrome, intermittent claudication, epilepsy, depression, Parkinson's disease, glaucoma. Use in pregnancy is discouraged. Moxonidine passes into breast milk. Excess mortality seen in patients with symptomatic heart failure.1 Side-effects Noteworthy side effects include dry mouth, headache, fatigue, dizziness, nausea, sleep disturbances rarely sedation, asthenia, vasodilatation, and rarely, skin reactions. References ^ Cohn J et al. 2003. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure MOXCON. Eur J Heart Fail 5 5: 659-67. doi:10.1016/S1388-98420300163-6. PMID 14607206. v d e Antihypertensives C02 and diuretics C03 Sympatholytic agents Centrally acting/antiadrenergics α2 agonist Clonidine, Guanfacine, Methyldopa imidazoline receptor agonist Moxonidine, Rilmenidine adrenergic uptake inhibitor Rescinnamine, Reserpine Ganglion-blocking/nicotinic antagonist Mecamylamine, Trimethaphan Peripherally acting/antiadrenergics α1 blockers: Prazosin Indoramin Trimazosin Doxazosin Urapidil Guanidine derivatives: Betanidine Guanethidine Guanoxan Debrisoquine Guanoclor Guanazodine Guanoxabenz Vasodilators Diazoxide hydrazinophthalazine Hydralazine, Dihydralazine, Endralazine, Cadralazine Minoxidil Nitroprusside Phentolamine Other antihypertensives serotonin antagonist Ketanserin endothelin receptor antagonist Bosentan, Ambrisentan, Sitaxsentan MAOI Pargyline THI Metirosine Diuretics Low ceiling Thiazides at DCT Bendroflumethiazide Hydroflumethiazide Hydrochlorothiazide Chlorothiazide Polythiazide Trichlormethiazide Cyclopenthiazide Methyclothiazide Cyclothiazide Mebutizide Sulfonamides Quinethazone Clopamide Chlortalidone Mefruside Clofenamide Metolazone Meticrane Xipamide Indapamide Clorexolone Fenquizone Other Mersalyl Theobromine Cicletanine osmotic Mannitol, Urea carbonic anhydrase inhibitor at PT Acetazolamide High ceiling Loop diuretic at AL Bumetanide, Furosemide, Torasemide, Ethacrynic acid Potassium-sparing at CD ESC blockers Amiloride, Triamterene aldosterone antagonists Spironolactone, Eplerenone, Potassium canrenoate, Canrenone Retrieved from http://en..org/wiki/Moxonidine Categories: Antihypertensive agents | Imidazolines | Pyrimidines Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Hrvatski Magyar This page was last modified on 31 July 2008, at 17:49
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