LOPHOTOXINS - IRREVERSIBLE ACTIVE-SITE-DIRECTED INHIBITORS OF NICOTINIC ACETYLCHOLINE-RECEPTORS

The lophotoxins are a family of structurally-related neurotoxins that can be isolated from various species of marine soft coral. Like many other naturally occurring neurotoxins, they inhibit nicotinic acetylcholine receptors, resulting in neuromuscular paralysis. However, they are unlike other nicotinic acetylcholine receptor antagonists in several respects. For instance, they do not contain a positive charge common to most cholinergic antagonists; they are conformationally constrained; they react covalently with a specific amino acid (Tyr190) in the alpha-subunit of the receptor; and they inhibit both neuronal and muscle subtypes of the receptor. These features make the lophotoxins useful probes for understanding the structure and function of neuronal and muscle nicotinic acetylcholine receptors. Their unique activity may also prove to be useful in a variety of clinical applications.