H1-Antagonists with nonclassical structure

SYNTHESIS AND DRUG PROFILE

H₁-Antagonists with nonclassical structure

1. Astemizole (Histalong)

Synthesis

Properties and uses: Astemizole is a white powder, practically insoluble in water, soluble in methylene chloride, methanol, and in alcohol. The drug is found to be more potent and possesses longer duration of action than the terfenadine. It has a slow onset, is long acting, and nonsedating piperidine antihistaminic having practically little anticholinergic activity. It is indicated for seasonal allergic rhinitis and chronic utricaria. It is an effective antiallergic agent giving protection against asthma, hay fever, and chronic urticaria. It does not exhibit any noticeable CNS activity.

Assay: Dissolve the sample in a mixture of anhydrous acetic acid and methyl ethyl ketone, and titrate against 0.1 M perchloric acid using naphtholbenzein solution as an indicator.

Dose: Usual dose is 10 mg (oral) increased, if required, to 30 mg per day for upto 7 days 1 h before meals. It is not recommended for children below 6 years.

2. Tazifylline

Properties and uses: Tazifylline is proved for its successful antiallergic activity, with no significant occurrence of side effects (dryness of mouth and sedation) and long duration of action.

3. Azelastine

Properties and uses: It is a racemic mixture of white crystals, soluble in water, methanol or propylene glycol, but only slightly soluble in ethanol, octanol, or glycerine. It combines potent H1-receptor antagonism with a negligible anticholinergic and moderate serotonergic activity. It is used in the treatment of itching of the eyes associated with allergic conditions.