Bipariden

Absorption

87% bioavailability

Toxicity

LD50=760 mg/kg (Orally in rats). Signs of overdose include dilated and sluggish pupils, warm, dry skin, facial flushing, decreased secretions of the mouth, pharynx, nose, and bronchi, foul-smelling breath, elevated temperature, tachycardia, cardiac arrhythmias, decreased bowel sounds, urinary retention, delirium, disorientation, anxiety, hallucinations, illusions, confusion, incoherence, agitation, hyperactivity, ataxia, loss of memory, paranoia, combativeness, and seizures.

Originator

Akineton HCl,Knoll,US,1959

The Uses of Bipariden

amoebicide

Background

A muscarinic antagonist that has effects in both the central and peripheral nervous systems. It has been used in the treatment of arteriosclerotic, idiopathic, and postencephalitic parkinsonism. It has also been used to alleviate extrapyramidal symptoms induced by phenothiazine derivatives and reserpine.

Indications

For use as an adjunct in the therapy of all forms of parkinsonism and control of extrapyramidal disorders secondary to neuroleptic drug therapy.

Definition

ChEBI: N-Propylpiperidine in which the methyl hydrogens are substituted by hydroxy, phenyl, and 5-norbornen-2-yl groups. A muscarinic antagonist affecting both the central and peripheral nervous systems, it is used in the treatment of all form of Parkinson's disease.

Manufacturing Process

65 grams of 3-piperidino-1-phenyl propanone-1 of the summary formula C14H29ON, produced according to Mannich's reaction by reacting acetophenone with formaldehyde and piperidine hydrochloride are dissolved in 300 cc of benzene. The resulting solution is added to an organo-magnesium solution prepared from 96 grams of [δ5-bicyclo-(2,2,1)-heptenyl-2]-chloride (also known as 5-chloro-2-norbomene) 18.5 grams of magnesium shavings, and 300 cc of ether.
The reaction mixture is boiled for half an hour under reflux. Thereafter the ether is removed by distillation, until the inside temperature reaches 65°- 70°C. The resulting benzene solution is added to 95 cc concentrated hydrochloric acid containing ice for further processing. Thereby, 3-piperidino- 1-phenyl-1-[δ5-bicyclo-(2,2,1)-heptenyl-2]-propanol-1 of the summary formula C21H29ON is obtained. The compound melts at 101°C and its chlorohydrate has a melting point of about 238°C. The compound is difficultly soluble in water, slightly soluble in ethanol, and readily soluble in methanol.

brand name

Akineton (Abbott).

Therapeutic Function

Antiparkinsonian

General Description

Biperiden,α-5-norbornen-2-yl- -phenyl-1-piperidinepropanol (Akineton), introduced in 1959,has a relatively weak visceral anticholinergic, but a strongnicotinolytic, action in terms of its ability to block nicotineinducedconvulsions. Therefore, its neurotropic action israther low on intestinal musculature and blood vessels. It hasa relatively strong musculotropic action, which is aboutequal to that of papaverine, in comparison with most syntheticanticholinergic drugs. Its action on the eye, althoughmydriatic, is much lower than that of atropine. These weakanticholinergic effects add to its usefulness in Parkinson syndromeby minimizing side effects.

Pharmacokinetics

Biperiden is a weak peripheral anticholinergic agent. It has, therefore, some antisecretory, antispasmodic and mydriatic effects. In addition, biperiden possesses nicotinolytic activity. The parenteral form of biperiden 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 biperiden, these drug-induced disturbances are rapidly brought under control.

Clinical Use

Biperiden is used in all types of Parkinson disease (postencephalitic,idiopathic, arteriosclerotic) and helps toeliminate akinesia, rigidity, and tremor. It is also usedin drug-induced extrapyramidal disorders to eliminatesymptoms and permit continued use of tranquilizers.Biperiden is also of value in spastic disorders not related toparkinsonism, such as multiple sclerosis, spinal cord injury,and cerebral palsy. It is contraindicated in all formsof epilepsy.

Safety Profile

Poison by ingestion,subcutaneous, intraperitoneal, and intravenous routes.When heated to decomposition, it emits toxic fumes ofNOx.

Synthesis

Biperiden, 1-(5-norbornen-2-yl)-1-phenyl-3-piperidinopropan-1-ol (10.2.4), is also synthesized according to the method of making trihexyphenidyl, except by reacting 2-(1-piperidino)propiophenone (10.2.1) with 5-norbornen-2-ylmagnesiumbromide [33,34].

Metabolism

The metabolism of biperiden is not completely understood, but does involve hydroxylation.