Abstract:
:Initially it was considered that moxonidine, like clonidine, acted at central (2)-adrenoceptors to reduce blood pressure. With the characterisation of imidazoline binding sites distinct from (2)-adrenoceptors, the consensus became that moxonidine was acting predominantly at imidazoline I(1) receptors in the rostral ventrolateral medulla to lower blood pressure. Moxonidine acts at prejunctional (2)-adrenoceptors on sympathetic nerve endings to decrease noradrenaline release and this may contribute to its ability to lower blood pressure. The predominant site of action of moxonidine may also depend on route of administration, with imidazoline I(1) receptors being predominant after central, and (2)-adrenoceptors predominant after systemic administration. The controversy over the mechanism and site of action with moxonidine is ongoing. In animal models, moxonidine lowers blood pressure, reduces cardiac hypertrophy and remodelling, reduces cardiac arrhythmias and increases blood flow in cerebral ischaemia. Moxonidine also has beneficial effects in animal models of diabetes and kidney disease. Moxonidine increases sodium and water excretion in rats, but not humans. Animal studies indicate that moxonidine may be useful in the treatment of glaucoma by reducing intra-ocular pressure. Animal studies show that moxonidine may also be effective in pain and in ethanol withdrawal. In humans, the pharmacokinetics of moxonidine are of the one-compartment model with first-order absorption. Renal elimination is the major route of elimination and individual titration of moxonidine is needed in patients with renal impairment. There is overwhelming evidence that moxonidine is a safe and effective antihypertensive. A large clinical trial of moxonidine in heart failure, MOXCON, was stopped because of excessive deaths in the moxonidine group. Moxonidine should not be used in patients with heart failure, but there are no obvious reasons to stop its use as an antihypertensive, or its development for other clinical uses.
journal_name
Expert Opin Pharmacotherjournal_title
Expert opinion on pharmacotherapyauthors
Doggrell SAdoi
10.1517/14656566.2.2.337keywords:
subject
Has Abstractpub_date
2001-02-01 00:00:00pages
337-50issue
2eissn
1465-6566issn
1744-7666journal_volume
2pub_type
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