Low molecular hydrophilic amino acid most probably without capacity for PXR/CAR-activation. Very rapidly bio transformed in the liver, probably via non-Cyp metabolism, Very low plasma levels and no capacity for significant pharmacokinetic drug interactions. The histaminergic, serotoninergic and dopaminergic pharmacodynamic actions are most probably without significance with regard to the hepatic state of ALAS1-induction. Gastrointestinal side effects may motivate attention to the caloric intake of the patient.

N-metyl pyridine ethane amine. M=136. The formula and molecular structure differs from histidine. Administered as dihydrochloride salt. Very soluble in water.

Indications: Vertigo e.g. in Mb Menire. Obesity management. (Hypertension and atypical depression). Per oral administration, Initial dose usually 8-18 mg 3 times daily, maintenance dose 24-48 mg/d. Histaminergic and possibly serotonergic and dopaminergic amino acid. Two modes of action. The stimulating effect inner ear blood vessel histamine H1-receptors giving rise to vasodilatation and increased permeability, helping to reverse inner ear endolymphatic hydrops in Mb Meneire. It also have powerful agonistic effects on histamine H3 receptors, the subsequent histamine release augmenting the direct agonistic H1 receptor effects of betahistidine. It is also postulated that betahistidine gives rise to a rise of 5-HT (serotonine) in the brain stem. Physiological effects of possible relevance to acute porphyria: Nausea, decreased appetite with weight loss may reduce caloric intake. The metabolic mainly histaminic side effects are without significance in the activation of acute porphyria. Confounding side effects: The confounding side effects are generally secondary to the histaminergic action of betahistidine: Nasuea, vomiting, diarrhoea, stomach cramping, usually not serious and subsiding between doses. Nervous system side effects include convulsions, confusion, hallucinations, tingling, numness and burning sensations. Shortness of breath and laboured breathing may take place.

Significant first-pass metabolism.

Rapidly and completely absorbed in all parts of the digestive tract. Plasma protein binding is very low. Immediately metabolized in the liver to amino ethyl pyridine and hydroxyethyl pyridine, and excreted in urine as pyridyl acetic acid. Very low plasma steady state plasma concentrations of the active substance, below the detection range 100 pg/mL.

Uneventful use reported in 2 patients with acute porphyria.