What Is Moxonidine?

Massonidine, also known as Massonidine, chemical name is 4-chloro-N- (4,5-dihydro-1H-imidazol-2-yl) -6-methoxy-2-methyl-5-pyrimidine Amine, molecular formula is C9H12ClN5O, molecular weight is 241.67700 density: 1.52g / cm3, boiling point: 364.7 ° C at 760 mmHg, flash point: 174.3 ° C, crystal, melting point 217-219 ° C (decomposition).

Chinese name: Mosonidine
Foreign name: Moxonidinum

CAS number: 75438-57-2
Molecular formula: C9H12ClN5O

Brief introduction to msonidine compounds

Mosonidin Basic Information

Chinese name SON

Chinese alias: Moxonidine without hydrochloric acid; 4-chloro-N- (4,5-dihydro-1H-imidazol-2-yl) -6-methoxy-2-methyl-5-pyrimidinamine; Moxonidine

English name: Moxonidinum

English alias: 4-chloro-N- (4,5-dihydro-1H-imidazol-2-yl) -6-methoxy-2-methylpyrimidin-5-amine Lomox; Norcynt; [14C] -Moxonidine; 4-chloro- 5-[(4,5-dihydro-1H-imidazol-2-yl) -amino] -6-methoxy-2-methylpyrimidine; Moxonidinum [Latin];

CAS number: 75438-57-2

Molecular formula: C ₉ H ₁₂ ClN ₅ O

Molecular weight: 241.67700

Structural formula:

Exact mass: 241.007300

PSA: 71.43000

LogP: 0.65550 ^[1]

Mosoni's physicochemical properties

Appearance and properties: crystal

Density: 1.52 g / cm ³ (20ºC)

Melting point: 40-43 ° C (lit.)

Boiling point: 364.7ºC at 760 mmHg

Flash point:> 230 ° F

Refractive index: 1.68

Storage conditions: Store in a cool, dark place in the original container. ^[1]

Massonidin production method

1: Mosonidin method 1:

The reaction of 5-amino-4,6-dichloro-2-methylpyrimidine and 1-acetyl-2-imidazolin-2-one resulted in the formation of msonidine by sodium methoxide. ^[1]

2: Mosonidin method 2:

5-Amino-4-chloro-6-methoxy-2-methylpyrimidine is reacted with ammonium thiocyanate and benzoyl chloride to obtain (I). Debenzoyl is obtained (II), methylated to obtain (III), and then treated with ethylenediamine to obtain moxonidine. ^[1]

Mosonidin

Works by stimulating central presynaptic 2-receptors. Its antihypertensive effect is similar to the calcium antagonist nifedipine and the ACE inhibitor captopril. For essential hypertension. ^[1]

Mosoni pharmacology and toxicology

1. Moxonidine 1.Pharmacological effects

Pharmacological effects This product is a central antihypertensive drug. It has a high affinity for the imidazoline I1 receptor, and is a selective agonist of the imidazoline I1 receptor. By stimulating the medullary imidazoline receptor, peripheral sympathetic nerve activity is reduced, vasodilation, and peripheral vascular resistance are reduced, thereby reducing blood pressure. The affinity of this product for 2 receptor is weaker than that for II imidazoline receptor. Therefore, this product does not slow down the heart rate and has no obvious central sedation effect when lowering blood pressure. ^[2]

2. Moxonidine 2. Toxicology Study

Pharmacological experiments in mice show that: this product can reduce the number of autonomous activities, cooperate with pentobarbital to promote sleep in mice, and inhibit central nervous system activity; it reduces heart rate while lowering blood pressure, but has no significant effect on ECG and respiratory frequency and depth influences. LD50 (half-lethal dose) of one gastric administration was 190mg / kg; LD50 of one intravenous injection was 37mg / kg; histological examination of dead mice revealed no significant changes in the other organs except for left ventricular dilatation and pulmonary vasodilation and congestion. ^[2]

Toxicity experiments in rats show that with the increase of the dose used, general drug reactions such as loose hair, less movement and slow weight gain; abnormal urine tests; elevated liver enzymes; pathological and histological abnormalities are mainly found in the kidney and heart. Most abnormal indicators can be recovered after four weeks of withdrawal.
The mutagenicity test showed that Moxonidine did not cause a significant increase in the number of retrograde colonies of each strain of the Ames test. No increase in the chromosome aberration rate of CHL cell lines was observed. Significant changes and the results were negative. It is suggested that the drug may cause less genetic mutation in vitro and chromosomal aberration in vivo. Reproductive toxicity tests have shown that this product has not been found to have teratogenic effects. ^[2]

Mosonidin Pharmacokinetics

This product absorbs quickly when taken orally, its blood concentration reaches 0.3 to 1 hour, and its bioavailability is about 88%. This product has no first-pass effect, 58-60% of the prototype compound is excreted by the kidney, and less than 2% of the drug is excreted by feces. Less than 15% of the drugs are metabolized in the body. The main products are 4,5-deoxymoxidine and guanidyl derivatives. Oral T1 / 2 (elimination half-life) is about 2 hours. Food intake does not affect the pharmacokinetics of this product. ^[2]

Moxonidine indications

Mild to moderate essential hypertension. ^[2]

Mosonidin precautions

When this product is combined with this blocker, if the heart is interrupted, the body blocker should be stopped first, and this product should be stopped after a few days.
Patients with renal insufficiency should reduce the dose and monitor blood pressure as prescribed by the doctor.
Discontinue medication when you are allergic to this product.

Although there has not been any abnormal change in blood pressure elevation during the use of this product, it is recommended not to take sudden withdrawal measures when taking this product for a long time.
Those driving or manipulating machines should be cautious and may affect their ability to drive or manipulate. ^[2]

Moxidine for pregnant and lactating women:

Disable this product.

Moxidine for children:

Children under 16 are disabled.

Moxonidine for the elderly:

Elderly patients should be used with caution and the initial dose should be small because their sensitivity to the drug is sometimes difficult to estimate. ^[2]

Mosonidin dosage

This product should adopt the principle of individualized medication. Generally start with the lowest dose, 0.2mg, once a day, and take it in the morning. Dosage adjustments should be made at three-week intervals until satisfactory results are obtained. The usual dose is 0.2 mg once, twice a day (morning and evening). The maximum daily dose should not exceed 0.4 mg, and the maximum daily dose should not exceed 0.6 mg. For patients with mild to moderate renal insufficiency, the single dose should not exceed 0.2 mg or the daily dose should not exceed 0.4 mg. ^[2]

Moxidine overdose

Overdose of this product may cause headache, sedation, drowsiness, hypotension, fatigue, weakness, bradycardia, dry mouth, vomiting and stomach pain, and hypertension, tachycardia and hyperglycemia may also occur. There is no special antidote for this product. When overdose is found, it should be treated symptomatically. When severe hypotension occurs, supine position should be taken and the lower limbs raised, blood volume should be replenished, blood pressure changes should be monitored, and vasoconstrictor drugs can be slowly injected intravenously if necessary. ^[2]

Moxonidine adverse reactions

Symptoms such as dry mouth, fatigue, and headache may appear at the beginning of treatment; occasionally dizziness, insomnia, and lower limb weakness may occur. Very few gastrointestinal discomforts, and individual skin allergic reactions.

Moxidine has a low incidence of adverse reactions, with about 15% -20% of patients complaining of dry mouth, which usually occurs within a few weeks of treatment initiation, which can gradually disappear with continued medication. In addition, there are fatigue, hyperactivity, headache, dizziness, and spontaneous dystonia. The results of the comparative study showed that the incidence of adverse reactions was much less than that of the first-generation central antihypertensive drug clonidine. ^[2]

Mosonidin contraindications

Under the following circumstances, it is strictly prohibited to take misonidine hydrochloride tablets.

Allergic to this product

2. Sinus node syndrome, Grade II and Grade III sinoatrial or atrioventricular block.

3. Sinus bradycardia, heart rate (50 beats / min) at rest.

4. Patients with malignant arrhythmia and moderate coronary insufficiency.

5. Patients with severe cardiac insufficiency.

6. Patients with unstable angina pectoris.

7. Patients with severe liver disease.

8. Patients with advanced renal dysfunction (GFR glomerular filtration rate is less than 30 ml per minute, and serum creatinine concentration is higher than 1.8 ml / 100 ml).

9. Patients with angioedema.

10. Patients with intermittent claudication.

11. Patients with Raynaud's disease.

12. Patients with tremor palsy (Parkinson's disease).

13. People with epilepsy.

14. Patients with glaucoma.

15. Patients with depression. ^[2]

Moxonidine Drug Interactions

1 When combined with beta blockers, hypotension occurs at the beginning, and then a strong rebound phenomenon occurs.

2 Combined with other antihypertensive drugs can enhance the antihypertensive effect of this product.

3 When combined with benzazoline, it can weaken the hypotensive effect of this product.

4 When combined with alcohol, sedatives or anesthetics, it can enhance its antihypertensive effect.

5 This product should not be used with tricyclic antidepressants. ^[2]

Mossudine Expert Reviews

This product is an 2-receptor agonist and belongs to the imidazoline antihypertensive drug. For moderate and severe primary and secondary hypertension. Because it inhibits the secretion and movement of the gastrointestinal tract, it is also suitable for hypertensive patients with ulcers. This medicine combined with diuretics can significantly improve the efficacy. It is a powerful central antihypertensive drug and a second-line antihypertensive drug. It is mainly administered locally in ophthalmology. This product has the effect of reducing intraocular pressure without affecting the pupil and eye adjustment mechanism. It can shrink the blood vessels in the eye, reduce the production of aqueous humor, and achieve the effect of reducing intraocular pressure. It starts to work 15 minutes after eye drops, and can maintain the effect for about 8 hours. ^[3]