Moxonidine

Description

Moxonidine, also known as Physiotens, is a highly selective imidazoline receptor agonist-Ⅰ by excitement ventrolateral medulla nucleus (RVLM)-Ⅰ type imidazoline receptor in the peripheral sympathetic nerve activity decreased. 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.
It is a new type of antihypertensive drug, commonly used in the treatment of essential hypertension. 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.
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.

Physical and Chemical Properties

ensity: 1.52g/cm3, boiling point:  364.7 °C at 760 mmHg, flash point: 174.3 °C, crystallization, melting point: 217-219 degrees Celsius.

Application

• By stimulating the central presynaptic alpha 2-receptor and onset, and its antihypertensive effect of ACE inhibitors, calcium antagonists nifedipine and captopril similar. Treatment of essential hypertension.
• The intervention of renal interstitial fibrosis can protect the kidney.

Preparation

5-amino-4,6-dichloro-2-methyl pyrimidine and 1-acetyl-2-imidazolin-2-one. The product, reacting with sodium methanol can produce moxonidine.

Precautions

• There may be dry mouth, fatigue and headache at the beginning of treatment, occasional dizziness, insomnia, and weakness in the legs and so on.
• Sick sinus syndrome, the sinus node and atrioventricular Ⅱ-Ⅲ degree block, resting bradycardia (50 beats/min), unstable angina, severe liver disease, progressive renal dysfunction, angioedema patients should not use it.

References

https://en.wikipedia.org/wiki/Moxonidine

Description

Moxonidine, which is structurally related to clonidine, is a new centrally acting antihypertensive that acts as a stronger agonist at imidazole receptors and a weaker agonist at α2-adrenergic receptors than clonidine. It is also reported to have less side effects and a much reduced potential to produce a rebound in blood pressure on withdrawal. Clinically, moxonidine appears to have comparable antihypertensive efficacy with the ACE inhibitors and calcium antagonists.

Chemical Properties

White Solid

Originator

Beiersdorf (Germany)

Uses

Antihypertensive;Imidazoline receptor agonist

Uses

Moxonidine is an antihypertensive agent.

Definition

ChEBI: Moxonidine is an organohalogen compound and a member of pyrimidines.

brand name

Cynt (Lilly); Nucynt (Lilly); Norcynt (Lilly);Physiotens.

Biological Activity

Mixed I 1 imidazoline receptor and α 2 -adrenergic agonist; displays 40-fold higher affinity for I 1 receptors versus α 2 -adrenoceptors. Centrally acting antihypertensive agent.

Clinical Use

Antihypertensive agent (centrally acting agonist at I1 receptor, imidazoline and alpha2 adrenoceptors)

Synthesis

Example 1 - Improved method for the preparation of crude moxonidine: a mixture of 4,6-dichloro-2-methyl-5-(1-acetyl-2-imidazolin-2-yl)aminopyrimidine (5 g, 0.0174 mol) with 85% potassium hydroxide powder (1.276 g, 0.019 mol, 1.1 eq.) in methanol (40 ml) was stirred at ambient temperature for 30 hours. Subsequently, water (50 ml) was added and stirring was continued for 1 hour. The colorless precipitate was collected by filtration, washed sequentially with water (3 x 10 ml) and 2-propanol (3 x 10 ml), and finally dried at 50 °C overnight to give 3.5 g of crude moxonidine in 83.5% yield and 98.2% purity (HPLC analysis).

Metabolism

10-20% metabolised, predominantly to 4,5-dehydromoxonidine and to an aminomethanamidine derivative both of which are much less active than moxonidine. Moxonidine and its metabolites are almost entirely eliminated via the kidney. More than 90% of the dose is eliminated in the first 24 hours via the kidney, while approximately 1% is eliminated in the faeces

References

[1] Patent: EP1894926, 2008, A1. Location in patent: Page/Page column 7
[2] Patent: US4323570, 1982, A