bisbenzylisoquinoline

Bisbenzylisoquinoline refers to a class of dimeric isoquinoline alkaloids in which two isoquinoline units are linked to form a bisbenzylisoquinoline framework. The best-known member is d-tubocurarine, a prototypical bisbenzylisoquinoline alkaloid historically derived from curare preparations used by indigenous peoples of South America and later investigated for medical use. These compounds are typically disubstituted to give two benzylisoquinoline moieties and often exist as salts that carry multiple positive charges at physiological pH, contributing to their solubility and interaction with biological targets.

Natural occurrence and notable members

Bisbenzylisoquinoline alkaloids occur in plants of families such as Menispermaceae. d-Tubocurarine from Chondrodendron tomentosum is the most prominent example and gave curare its ethnobotanical and pharmacological fame. Other members of the class have been identified in related plant sources, displaying varying substitutions on the isoquinoline rings.

Pharmacology and medical use

These compounds are known for their potent neuromuscular blocking properties. They act as competitive antagonists of nicotinic acetylcholine receptors at the motor endplate, producing flaccid paralysis. Because they are quaternary ammonium compounds, they are not orally active and are typically used parenterally in medical settings to facilitate anesthesia and endotracheal intubation. Adverse effects can include histamine release and hypotension. Recovery and reversal of blockade are achieved with agents such as acetylcholinesterase inhibitors, often supplemented with anticholinergic drugs to offset muscarinic effects. Due to the development of shorter-acting and more selective neuromuscular blockers, older bisbenzylisoquinolines like tubocurarine have largely been supplanted in routine practice, though they remain important for historical and pharmacological study.

Synthesis and research

In nature, these alkaloids arise from biosynthetic pathways pairing two isoquinoline units; synthetic efforts have produced various analogs to study receptor interactions and structure-activity relationships.