Dibenzocyclo heptene derivatives

SYNTHESIS AND DRUG PROFILE 

H₁-antagonists with classical structure 

Dibenzocyclo heptene derivatives 

1. Cyproheptadine (Periacetin)

Properties and uses: Cyproheptadine hydrochloride is a white or slightly yellow crystalline powder, slightly soluble in water and methanol, sparingly soluble in alcohol. This dibenzocycloheptene may be regarded as a phenothiazine analogue in which the sulphur atom has been replaced by an isosteric vinyl group and the ring nitrogen replaced by a sp² carbon atom. It also possesses antiserotonin activity and is used as an antipruritic agent associated with skin disorders (utricaria, allergic dermatitis, neurodermatitis). It is used to stimulate the appetite in under-weight patients and those suffering from anorexia nervosa.

Synthesis

Assay: Dissolve the sample in a mixture of 0.01 M hydrochloric acid and alcohol and titrate against 0.1 M sodium hydroxide. Determine end point potentiometrically.

Dose: Usually, the dose is 4 mg taken orally three times a day.

Dosage forms: Cyproheptadine HCl syrup I.P., Cyproheptadine HCl tablets I.P., Cyproheptadine tablets B.P.

2. Azatadine

Synthesis

Route I. From: 2-Chloro-3-phenethylpyridine

Route II. From: Phenylacetonitrile

Properties and uses: Azatadine is a potent, long-acting antihistaminic with antiserotonin activity. In early testing, azatadine exhibited more than three times the potency of chlorpheniramine in the isolated guinea pig ileum screening and more than seven times the oral potency of chlorpheniramine in the protection of guinea pig against a double lethal dose of intravenously administered histamine.

Azatadine is an aza isostere of cyproheptadine in which the 10, 11-double bond is reduced. It has low sedative effect.