Dimezine Mechanism of Action

Antihistamine (Aminoalkyl ether)/Antivertigo.
Pharmacology: Pharmacodynamics: Dimenhydrinate, the chlorotheophylline salt of diphenhydramine, acts as antihistamine with anticholinergic (antimuscarinic) properties, exerting parasympatholytic and centrally-depressant effects. The substance exhibits antiemetic and antivertiginous effects through influencing the chemoreceptor trigger zone in the region of the 4th ventricle. Dimenhydrinate thus acts predominantly on the central vestibular system.
Due to its calcium antagonistic properties, cinnarizine acts mainly as a vestibular sedative through inhibition of the calcium influx into the vestibular sensory cells. Cinnarizine thus acts predominantly on the peripheral vestibular system.
Both cinnarizine and dimenhydrinate are known to be effective in the treatment of vertigo. The combination product is more effective than the individual compounds in the population studied. The product has not been evaluated in motion sickness.
Pharmacokinetics: Absorption and Distribution: Dimenhydrinate rapidly releases its diphenhydramine moiety after oral administration. Diphenhydramine and cinnarizine are rapidly absorbed from the gastro-intestinal tract. Maximum plasma concentrations (Cmax) of cinnarizine and diphenhydramine are reached in humans within 2-4 hours. The plasma elimination half-lives of both substances range from 4-5 hours, when given either alone or as the combination product.
Biotransformation: Cinnarizine and diphenhydramine are extensively metabolised in the liver. The metabolism of cinnarizine involves ring hydroxylation reactions that are in part catalysed by CYP2D6 and N-desalkylation reactions of low CYP-enzyme specificity. The main pathway in the diphenhydramine metabolism is the sequential N-demethylation of the tertiary amine. Studies in human liver microsomes in vitro indicate the involvement of various CYP-enzymes, including CYP2D6.
Elimination: Cinnarizine is mainly eliminated via the faeces (40-60%) and to a lower extent also in urine, mainly in the form of metabolites conjugated with glucuronic acid. The major route of elimination of diphenhydramine is in the urine, mainly in the form of metabolites, with the deaminated compound, diphenylmethoxy acetic acid, being the predominant metabolite (40-60%).