Each AKINETON tablet for oral administration contains 2 mg biperiden hydrochloride. Other ingredients may include corn syrup, lactose, magnesium stearate, potato starch and talc. AKINETON is an anticholinergic agent. Biperiden is α-5-Norbornen-2-yl-α-phenyl-1-piperidinepropanol. It is a white, crystalline, odorless powder, slightly soluble in water and alcohol. It is stable in air at normal temperatures. Biperiden may be represented by the following structural formula:
AKINETON is a weak peripheral anticholinergic agent. It has, therefore, some antisecretory, antispasmodic and mydriatic effects. In addition, AKINETON possesses nicotinolytic activity. Parkinsonism is thought to result from an imbalance between the excitatory (cholinergic) and inhibitory (dopaminergic) systems in the corpus striatum. The mechanism of action of centrally active anticholinergic drugs such as AKINETON is considered to relate to competitive antagonism of acetylcholine at cholinergic receptors in the corpus striatum, which then restores the balance.
The parenteral form of AKINETON is an effective and reliable agent for the treatment of acute episodes of extrapyramidal disturbances sometimes seen during treatment with neuroleptic agents. Akathisia, akinesia, dyskinetic tremors, rigor, oculogyric crisis, spasmodic torticollis, and profuse sweating are markedly reduced or eliminated. With parenteral AKINETON, these drug-induced disturbances are rapidly brought under control. Subsequently, this can usually be maintained with oral doses which may be given with tranquilizer therapy in psychotic and other conditions requiring an uninterrupted therapeutic program.
Pharmacokinetics and Metabolism
Only limited pharmacokinetic studies of biperiden in humans are available. The serum concentration at 1 to 1.5 hours following a single, 4 mg oral dose was 4-5 ng/mL. Plasma levels (0.1-0.2 ng/mL) could be determined up to 48 hours after dosing. Six hours after an oral dose of 250 mg/kg in rats, 87% of the drug had been absorbed. The metabolism of AKINETON is also incompletely understood, but does involve hydroxylation. In normal volunteers a single 10 mg intravenous dose of biperiden seemed to cause a transient rise in plasma cortisol and prolactin. No change in GH, LH, FSH, or TSH levels were seen. Biperiden lactate (10 mg/mL) was not irritating to the tissue of rabbits when injected intramuscularly (1.0 mL) into the sacrospinalis muscles and intradermally (0.25 mL) and subcutaneously (0.5 mL) into the shaved abdominal skin.