Biperiden

Mechanism

Chemical and Commercial Profile

Common trade names: Akineton, Biperidene Normon.
Group: Antiparkinsonian, centrally acting muscarinic antagonist.

Mechanism of Action

Biperiden acts through **specific and competitive antagonism of muscarinic acetylcholine receptors** (mainly of the M₁ subfamily) located in the interneurons of the striatum. By blocking cholinergic transmission, it restores the relative balance between dopamine (which is decreased in Parkinson's) and acetylcholine (which is increased in a relative state of hyperactivity), reducing resting tremor and muscle rigidity.

Pharmacokinetics

Pharmacokinetics

• Absorption: Rapid after oral intake; bioavailability of 30% due to significant hepatic first-pass metabolism. The plasma peak is reached at 1.5 hours.
• Distribution: Very high binding to plasma proteins (90%). Large distribution volume of 24 L/kg. It quickly crosses the blood-brain barrier.
• Metabolism: Hepatic through oxidative hydroxylation catalyzed by multiple isoenzymes of cytochrome (CYP450). Produces inactive metabolites.
• Excretion: Renal (60%) and fecal (40%) mainly in the form of inactive conjugated metabolites.
• Half-life (t_1/2): 18 to 24 hours, ideal for administration divided into two or three daily doses.

Indicators and dose

Indications

• Treatment of Idiopathic Parkinson's Disease (especially useful to control difficult-to-manage rest tremor and persistent sialorrhea).
• Prevention and treatment of neuroleptic-induced extrapyramidal reactions (such as acute dystonias or severe akathisia) parenterally (IM/slow IV).

Dosage and Settings

• Initial Monotherapy (Oral): Start with 1 mg twice a day; gradually increase to a common range of 2-6 mg/day (maximum of 8 mg/day in three doses).
• Acute Extrapyramidal Reactions (IM / slow IV): Administer 2.5-5 mg by deep intramuscular or slow intravenous route, and may be repeated after 30 minutes if dystonia persists. Requires blood pressure monitoring and ECG.
• Renal / Hepatic Failure: No adjustments are required in moderate renal failure. In Child-Pugh B or C liver failure, extreme caution is recommended.

Security

Contraindications

• Uncontrolled acute narrow-angle glaucoma (due to the risk of causing massive mydriasis and critical elevation of intraocular pressure).
• Known benign prostatic hyperplasia (due to high risk of inducing severe acute urinary retention).
• Intestinal atony or toxic megacolon.

Adverse Effects (ADR)

Delirium and Falls Alert in the Elderly

The use of biperiden in elderly patients is associated with an extremely high risk of inducing **central anticholinergic type delirium, profound mental confusion, hallucinations, psychomotor agitation and secondary accidental falls**. Furthermore, a worsening in memory and global executive functions has been demonstrated by cortical acetylcholine blockade. Its regimen should be strictly avoided in patients over 65 years of age.

• Anticholinergics: Severe xerostomia (dry mouth that makes swallowing difficult), blurred vision due to impaired ocular accommodation (cycloplegia), refractory motor constipation, acute urinary retention, decreased sweating (with risk of heatstroke), sinus tachycardia.
• CNS: Visual hallucinations, confusion, drowsiness, fatigue.

Clinical Interactions

• Tricyclic Antidepressants: Amitriptyline or clomipramine additively enhance the anticholinergic effects of biperiden, potentially triggering paralytic ileus or intestinal obstruction.
• Neuroleptics / Antipsychotics: Clozapine or quetiapine potentiate central side effects, requiring close monitoring of levels of consciousness.

Pregnancy and Breastfeeding

FDA Category: C. Very limited human data; It is absolutely not recommended during pregnancy due to systemic ophthalmic restriction. Breastfeeding: Absolutely contraindicated. Like other dopaminergic drugs, it potently inhibits pituitary prolactin release reflexively, suppressing lactation, in addition to being excreted in breast milk.