Betacitam

Uses

Betahistine Mesilate dilates precapiilary sphincters, increasing the blood flow in the inner ear. It controls the permeability of capillaries in the inner ear, thereby removes endolymphatic hydrops. It also improves cerebral circulation, increasing blood flow in the internal carotid artery. Thus, Betahistine Mesylate is clinically useful for the relief of vertigo and dizziness.

Ginkgo biloba is a herbal supplement found in over-the-counter or unapproved homeopathic products for various health conditions, such as cognitive, neurodegenerative, cardiovascular, and reproductive health disorders.

Ginkgo biloba does not currently have any approved therapeutic indications, and there is insufficient evidence to support its unapproved use. It is available in over-the-counter herbal products mostly for oral use, to improve memory and cognitive problems.

Betacitam is also used to associated treatment for these conditions: Menière's DiseaseCognitive Dysfunctions, Cognitive Function, Depression

How Betacitam works

Vertigo is a disturbing sensation of movement caused by dysfunction of the labyrinth (inner ear), vestibular nerve, cerebellum, brainstem, or Central Nervous System (CNS). Vestibular forms of vertigo are often accompanied by auditory dysfunctions such as hyperacusis, hearing loss, and tinnitus. In most cases, adaptive mechanisms of the CNS lead to functional recovery after episodes of vertigo, however, syndromes such as Ménière's disease tend to cause the recurrence of vertigo symptoms. This significantly impacts the quality of life and the ability to carry out daily activities.

H1-receptor activity

The mechanism of action of betahistine is multifactorial. Ménière's disease is thought to result from a disruption of endolymphatic fluid homeostasis in the ear. Betahistine mainly acts as a histamine H1-receptor agonist. The stimulation of H1-receptors in the inner ear causes a vasodilatory effect leading to increased permeability of blood vessels and a reduction in endolymphatic pressure; this action prevents the rupture of the labyrinth, which can contribute to the hearing loss associated with Ménière's disease. Betahistine is also purported to act by reducing the asymmetrical functioning of sensory vestibular organs and increasing vestibulocochlear blood flow, relieving symptoms of vertigo.

H3-receptor activity

In addition to the above mechanisms, betahistine also acts as a histamine H3-receptor antagonist, increasing the turnover of histamine from postsynaptic histaminergic nerve receptors, subsequently leading to an increase in H1-agonist activity. H3-receptor antagonism elevates levels of neurotransmitters including serotonin in the brainstem, inhibiting the activity of vestibular nuclei, thus restoring proper balance and decreasing vertigo symptoms.

Two key active ingredients in ginkgo biloba are terpene lactones (notably ginkgolides and diterpenes) and ginkgo flavone glycosides (notably ginkgetin, bilobetin, and sciadopitysin), which are present at varying concentrations. Ginkgo biloba extract EGb 761 is the standardized extract of ginkgo biloba used in studies, which contains 6% terpenoids and 24% flavonoid glycosides. Animal studies have shown that ginkgo biloba works on several neurotransmitter pathways and brain structures. Flavones were shown to inhibit lipid peroxidation; inhibit the uptake of serotonin, dopamine, and norepinephrine; and inhibit platelet aggregation. Terpene lactones may also act as potent antagonists of the platelet-activating factor and may possess anti-ischemic and fibrinolytic effects. They were also shown to downregulate adrenal peripheral benzodiazepine receptors and increase adrenocorticotropic hormone levels. Ginkgo biloba also reversibly inhibits monoamine oxidase A; and modestly inhibits anticholinesterase activity, leading to enhanced cholinergic transmission in the brain.

Several studies suggest that ginkgo biloba exerts neuroprotective effects by reducing free radical production in the prefrontal cortex, which may explain its improvement on short-term memory. Ginkgo biloba extract acts as a free radical scavenger, protecting neurons from oxidative damage and apoptosis related to aging, cerebral ischemia, and neurodegenerative disorders. Ginkgo biloba also inhibits amyloid-β neurotoxicity and protects against hypoxic challenges and increased oxidative stress. One study showed that bilobalide, a terpene lactone, delays the onset of hypoxic glycolysis. Ginkgo biloba has the potential to regulate metabolism, stabilize the membrane, and promote vasodilation. In the arterial endothelium, EGb stimulated the release of endogenous relaxing factors, such as endothelium-derived relaxing factor and prostacyclin. In the inflammatory environment that causes tissue damage, EGb promoted nitric oxide production, leading to enhanced peripheral and cerebral blood flow.

Dosage

Betacitam dosage

Usually for adults, administer orally 6 mg to 12 mg three times per day after meals. The dose may be adjusted according to the age of patient and severity of symptoms.

Side Effects

Nausea or vomiting may rarely occur. Hypersensitivity reactions, such as skin rash, may rarely occur.

Toxicity

Symptoms of an overdose with betahistine (< 640 mg) include dry mouth, nausea, dyspepsia, abdominal pain, and somnolence. Serious complications such as convulsions, pulmonary or cardiac effects may occur with higher doses (> 640 mg), especially during intentional overdoses and combination with other drugs. In the case of an overdose with betahistine, provide supportive therapy, and contact the local poison control center for further management.

Oral LD₅₀ of standardized extract in mice is 7730 mg/kg, which corresponds to 2300 mg/kg of active ingredients, 1900 mg/kg of flavone glycosides, and 464 mg/kg of terpene lactones. Intravenous LD₅₀ is 1100 mg/kg.

No case of overdose has been reported so far. Cyanogenic glycosides found in raw ginkgo seeds are potentially toxic compounds; thus, contact or ingestion of ginkgo seeds can lead to serious reactions such as allergic skin reaction, including acute generalized exanthematous pustulosis, and convulsions. Ginkgo toxicity can manifest as bleeding, seizure, and serotonin syndrome. As there is no known antidote for ginkgo toxicity, treatment includes discontinuation of ginkgo and symptomatic and supportive care. Seizures may be attributed to ginkgotoxin, which can cause seizures at high doses.

Precaution

Patients with a history of digestive ulcer or an active digestive ulcer, Patients with bronchial asthma, Patients with pheochromocytoma.

Volume of Distribution

In a pharmacokinetic study of rats, betahistine was found to be distributed throughout the body. Human data for betahistine's volume of distribution is not readily available.

No data available.

Elimination Route

When given orally, betahistine is rapidly and almost completely absorbed from the gastrointestinal tract. In the fasted state, Cmax is achieved within 1 hour of administration; in the fed state, Cmax is delayed, but the total drug absorption is similar. Food, therefore, has little effect on the absorption of betahistine.

Studies assessed the pharmacokinetic parameters of terpene lactones, the main component of ginkgo biloba. Following oral administration of ginkgo biloba solution, the mean absolute bioavailability was 80% for ginkgolide A, 88% for ginkgolide B and 79% for biloalide. In an early rat study, about 60% of radiolabeled EGb 761 was absorbed with a T_max of 1.5 hours. The highest amount of radioactivity was measured in the stomach and small intestine.

In another study, after a single oral dose of 120 mg EGb 761 in healthy volunteers, C_max was 22.22 ± 4.57 ng/mL for ginkgolide A, 8.27 ± 1.82 ng/mL for ginkgolide B, and 54.42 ± 13.62 ng/mL for biloalide. AUC_0-∞ was 121.35 ± 22.92 ng × h/mL for ginkgolide A, 59.88 ± 11.39 ng × h/mL for ginkgolide B, and 217.24 ± 44.07 ng × h/mL for biloalide. T_max ranged from 1.17 to 1.54 hours for those three compounds.

Half Life

The half-life of betahistine is 3-4 hours.

Unpublished human data reports that after oral administration of 80 mg EGb 761, the half-life was four hours for ginkgolides A and six hours for ginkgolides B. The half-life of bilobalide was three hours after administration of 120 mg EGb 761 extract.

Clearance

No data available.

Elimination Route

Betahistine is mainly excreted in the urine; with approximately 85-91% being detected in urine samples within 24 hours of administration.

At 72 hours following oral administration in rats, about 38% of the ginkgo biloba extract was excreted via expiration, 22% was excreted in urine, and 29% was excreted in feces. About 70% of ginkgolides A, 50% of ginkgolides B, and 30% of bilobalide were excreted unchanged in the urine.

Pregnancy & Breastfeeding use

Safety of Betahistine during pregnancy has not been established. This drug should be administered to pregnant patients or women suspected of being pregnant, only if the expected therapeutic benefit is thought to outweigh any possible risk.

Contraindication

Hypersensitivity to betahistine mesylate, pheochromocytoma, peptic ulcer, acute bronchial asthma.

Storage Condition

Store in cool and dry place. Protect from light & moisture.

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