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Verserc Actions |
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Pharmacotherapeutic Group: Antivertigo preparations.
Pharmacology: Pharmacodynamics: Mechanism of Action: The mechanism of action of Verserc is partly understood. There are several plausible hypotheses that are supported by animal studies and human data: Verserc Affects the Histaminergic System: Verserc acts both as a partial histamine H1-receptor agonist and histamine H3-receptor antagonist also in neuronal tissue, and has negligible H2-receptor activity. Verserc increases histamine turnover and release by blocking presynaptic H3-receptors and inducing H3-receptor downregulation.
Verserc may Increase Blood Flow to the Cochlear Region as well as to the Whole Brain: Pharmacological testing in animals has shown that the blood circulation in the striae vascularis of the inner ear improves, probably by means of a relaxation of the precapillary sphincters of the microcirculation of the inner ear. Verserc was also shown to increase cerebral blood flow to humans.
Verserc Facilitates Vestibular Compensation: Verserc accelerates the vestibular recovery after unilateral neurectomy in animals, by promoting and facilitating central vestibular compensation. This effect, characterized by an up-regulation of histamine turnover and release, is mediated through H3-receptor antagonism. In human subjects, recovery time after vestibular neurectomy was also reduced when treated with Verserc.
Verserc Alters Neuronal Firing in the Vestibular Nuclei: Verserc was also found to have a dose-dependent inhibiting effect on spike generation of neurons in lateral and medial vestibular nuclei.
The pharmacodynamic properties as demonstrated in animals may contribute to the therapeutic benefit of Verserc in the vestibular system.
The efficacy of Verserc was shown in studies in patients with vestibular vertigo and with Meniere's disease as was demonstrated by improvements in severity and frequency of vertigo attacks.
Pharmacokinetics: Absorption:
Orally administered Verserc is readily and almost completely absorbed from all parts of the gastrointestinal tract. After absorption, Verserc is rapidly and almost completely metabolized into 2-pyridyl acetic acid (2-PAA). Plasma levels of Verserc are very low.
Pharmacokinetic analyses are therefore based on 2-PAA measurements in plasma and urine.
Under fed conditions, maximum plasma concentration (Cmax) is lower compared to fasted conditions. However, total absorption of Verserc is similar under both conditions, indicating that food intake only slows down the absorption of Verserc.
Distribution: The percentage of Verserc that is bound by blood plasma proteins is <5%.
Biotransformation: After absorption, Verserc is rapidly and almost completely metabolized into 2-PAA (which has no pharmacological activity). After oral administration of Verserc, the plasma (and urinary) concentrations of 2-PAA reaches its maximum 1 hr after intake and decline with a half-life (t½) of about 3.5 hrs.
Excretion: 2-PAA is readily excreted in the urine. In the dose range of 8-48 mg, about 85% of the original dose is recovered in the urine. Renal or fecal excretion of Verserc itself is of minor importance.
Linearity: Recovery rates are constant over the oral dose range of 8-48 mg indicating that the pharmacokinetics of Verserc are linear, and suggesting that the involved metabolic pathway is not saturated.
Should be taken with food.
Verserc primarily acts as a histamine H1-agonist with 0.07 times the activity of histamine. Stimulating the H1-receptors in the inner ear causes a vasodilatory effect and increased permeability in the blood vessels which results in reduced endolymphatic pressure. Verserc is believed to act by reducing the asymmetrical functioning of sensory vestibular organs as well as by increasing vestibulocochlear blood flow. Doing so aids in decreasing symptoms of vertigo and balance disorders. Verserc also acts as a histamine H3-receptor antagonist which causes an increased output of histamine from histaminergic nerve endings which can further increase the direct H1-agonist activity. Furthermore, H3-receptor antagonism increases the levels of neurotransmitters such as serotonin in the brainstem, which inhibits the activity of vestibular nuclei, helping to restore proper balance and decrease in vertigo symptoms.
Users | % | ||
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With a meal | 1 | 50.0% | |
After food | 1 | 50.0% |
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Information checked by Dr. Sachin Kumar, MD Pharmacology
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