Blood pressure
High blood pressure accounts for 35–50% of stroke risk. Blood pressure reduction of 10 mmHg systolic or 5 mmHg diastolic reduces the risk of stroke by ~40%. Lowering blood pressure has been conclusively shown to prevent both ischemic and hemorrhagic strokes. It is equally important in secondary prevention. Even people older than 80 years and those with isolated systolic hypertension benefit from antihypertensive therapy. The available evidence does not show large differences in stroke prevention between antihypertensive drugs—therefore, other factors such as protection against other forms of cardiovascular disease and cost should be considered. The routine use of beta-blockers following a stroke or TIA has not been shown to result in benefits. Blood lipids
High cholesterol levels have been inconsistently associated with (ischemic) stroke. Statins have been shown to reduce the risk of stroke by about 15%. Since earlier meta-analyses of other lipid-lowering drugs did not show a decreased risk, statins might exert their effect through mechanisms other than their lipid-lowering effects. Diabetes mellitus
Diabetes mellitus increases the risk of stroke by 2 to 3 times. While intensive blood sugar control has been shown to reduce small blood vessel complications such as kidney damage and damage to the retina of the eye it has not been shown to reduce large blood vessel complications such as stroke. Anticoagulation drugs
Oral anticoagulants such as warfarin have been the mainstay of stroke prevention for over 50 years. However, several studies have shown that aspirin and other antiplatelets are highly effective in secondary prevention after a stroke or transient ischemic attack.
Meclizine also is a dopamine antagonist at D1-like and D2-like receptors but does not cause catalepsy in mice, perhaps because of its anticholinergic activity. Chemistry
Meclizine is a first-generation antihistamine (nonselective H1 antagonist) of the piperazine class. It is structurally and pharmacologically similar to buclizine, cyclizine, and hydroxyzine, but has a shorter half-life of six hours compared to cyclizine and hydroxyzine with about 20 hours (though half-life should not be confused with duration). It is used as an antivertigo/antiemetic agent, specifically in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Meclizine is sometimes combined with opioids, especially ones of the open-chain class like methadone, dextropropoxyphene, and dipipanone. Similarly, Diconal is a combination drug containing dipipanone and cyclizine. Synthesis
(4-Chlorphenyl)-phenylmethanol is halogenated with thionyl chloride before adding acetylpiperazine. The acetyl group is cleaved with diluted sulfuric acid. An N-alkylation of the piperazine ring with 3-methylbenzylchloride completes the synthesis. Alternatively, the last step can be replaced by a reductive N-alkylation with 3-methylbenzaldehyde. The reductive agent is hydrogen, and Raney nickel is used as a catalyst. Meclizine is obtained and used as a racemate, a 1:1 mixture of the two stereoisomers. Drug forms contain the racemic dihydrochloride. Names
Meclizine is an international nonproprietary name.It is sold under the brand names Bonine, Bonamine, Antivert, Postafen, Sea Legs, and Dramamine II (Less Drowsy Formulation). Emesafene is a combination of meclizine (1/3) and pyridoxine (2/3). In Canada, Antivert Tab (which is no longer available) was a combination of meclizine and nicotinic acid. Notes
References
External links
"Meclizine". Drug Information Portal.