Scientists have for the first time determined¹ the three-dimensional atomic structure of a human opioid（阿片样物质） receptor, a molecule² on the surface of brain cells that binds³ to opioids and is centrally involved in pleasure, pain, addiction⁴, depression, psychosis, and related conditions. Dozens of legal and illegal drugs, from heroin⁵ to hospital anesthetics（麻醉药） , work by targeting these receptors. The detailed⁶ atomic structure information paves the way for the design of safer and more effective opioid drugs. "This finding is going to have a major impact on understanding the fundamental principles of opioid receptor recognition and evolution," said Raymond Stevens, PhD, a professor at The Scripps Research Institute. Stevens is the senior author of the new study, which appears online in the journal Nature on March 21, 2012.

 A Symphony of Activity

Opioid receptor subtypes in the human brain work together in a symphony of activity that is still not fully⁷ understood. The "mu" opioid receptors mediate⁸ feelings of pleasure and pain-relief; they are the prime targets of the body's own endorphin neurotransmitters as well as heroin, morphine（吗啡） , and most other opioid drugs. By contrast, "kappa" opioid receptors are bound by neurotransmitters known as dynorphins, and when activated⁹ can depress mood and produce dissociative, psychedelic（迷幻剂） experiences. The plant Salvia divinorum, which was originally cultivated by Mesoamerican societies for religious ceremonies and is now used widely as a recreational drug, has an active ingredient, Salvinorin A, that binds selectively and with high affinity¹⁰ to kappa opioid receptors.

"We don't know why kappa receptors evolved, but we know that they have been around for a long time in evolutionary¹¹ terms; even frogs have them," said Bryan Roth, a professor of pharmacology and an opioid receptor expert at the University of North Carolina, whose group teamed with the Stevens lab for the new study.

If their psychedelic and mood-darkening effects could be avoided somehow, kappa opioid receptor activators, or "agonists," could be very useful medically. In animal studies, they act as mild and non-addicting pain-relievers, weaken the addictive¹² effects of other drugs, and reduce irritable¹³ bowel¹⁴ signs. "Antagonist¹⁵" compounds that block kappa opioid receptor activity also show promise as treatments for depression, anxiety, and other psychiatric conditions. Even the psychedelic effects associated with kappa receptor activation¹⁶ could be useful in providing insights into perception and consciousness. "This is a receptor that is important for how we see reality," said Roth.