Compounds that activate the brain’s anti-pain pathways — but have a limited effect on molecules that produce unpleasant side effects — could form the basis of a new class of drugs.
Researchers have been studying the brain’s κ-opioid receptor as a potential target for pain-relieving drugs. When this receptor is bound by messaging molecules, it activates two neural pathways: one reduces pain and itchiness, but the other produces side effects such as hallucinations.
The compound triazole 1.1 acts on this receptor to relieve pain and itching in mice without causing these side effects. To clarify the underlying mechanism, Laura Bohn at the Scripps Research Institute in Jupiter, Florida, and her colleagues treated mouse brain cells with triazole 1.1.
The team found that, compared with a compound that does cause side effects, triazole 1.1 triggered less movement of κ-opioid receptors into nerve cells. The presence of these receptors in the cells is a sign that molecules involved in causing side effects have been activated.
Triazole 1.1 and other ‘biased’ agents that primarily activate the anti-pain pathway could pave the way for the development of better opioids.