Salvinorin A, a naturally occurring hallucinogen as potent as LSD, works by selectively activating the kappa opioid receptor (KOR). It is unique among KOR agonists because it contains no nitrogen. This selectivity suggests the KOR could be a target for developing drugs to treat perception-related disorders such as schizophrenia, Alzheimer's disease, and bipolar disorder.
Salvinorin A, a hallucinogenic compound from the plant Salvia divinorum, selectively and potently activates kappa-opioid receptors (KORs), making it the only known lipid-like molecule to do so and the only non-nitrogenous opioid receptor agonist. Key residues in KORs responsible for its high binding affinity and agonist efficacy were identified: interactions with tyrosine residues in helix 7 (Tyr313 and Tyr320) and helix 2 (Tyr119) stabilize salvinorin A in the binding pocket, while activation requires interactions with helix 7 tyrosines Tyr312, Tyr313, and Tyr320 and with Tyr139 in helix 3.