6β-naltrexol 6β-naltrexol 6β-naltrexol, or 6β-hydroxynaltrexone (developmental code name aiko-150), is a peripherally-selective opioid receptor antagonist related to naltrexone. it is a major active metabolite of naltrexone formed by hepatic dihydrodiol dehydrogenase enzymes. with naltrexone therapy, 6β-naltrexol is present at approximately 10- to 30-fold higher concentrations than naltrexone at steady state due to extensive first-pass metabolism of naltrexone into 6β-naltrexol. in addition to being an active metabolite of naltrexone, 6β-naltrexol was itself studied for the treatment of opioid-induced constipation. it was found to be effective and well-tolerated, and did not precipitate opioid withdrawal symptoms or interfere with opioid pain relief, but development was not further pursued. 6β-naltrexolclinical dataother names6beta-naltrexol; 6β-hydroxynaltrexone; aiko-150; 17-(cyclopropylmethyl)-4,5α-epoxymorphinan-3,6α,14-trioldrug classopioid antagonistpharmacokinetic dataelimination half-life12–18 hoursidentifiers iupac name (4r,4as,7r,7ar,12bs)-3-(cyclopropylmethyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuroisoquinoline-4a,7,9-triol cas number49625-89-0pubchem cid5486554chemspider4588965uniij0w963m37tchemblchembl140278comptox dashboard (epa)dtxsid80197942 echa infocard100.230.713 chemical and physical dataformulac20h25no4molar mass343.423 g·mol−13d model (jsmol)interactive image smiles c1c2(3cc4=c52(ccn3cc6cc6)(1o)oc5=c(c=c4)o)o inchi inchi=1s/c20h25no4/c22-13-4-3-12-9-15-20(24)6-5-14(23)18-19(20,16(12)17(13)25-18)7-8-21(15)10-11-1-2-11/h3-4,11,14-15,18,22-24h,1-2,5-10h2/t14-,15-,18+,19+,20-/m1/s1key:jlvnehkorqfvqj-pyijolgtsa-n 6β-naltrexol binds to the opioid receptors with affinity (ki) values of 2.12 nm for the μ-opioid receptor (mor), 7.24 nm for the κ-opioid receptor (kor), and 213 nm for the δ-opioid receptor (dor). hence, 6β-naltrexol shows 3.5-fold selectivity for the mor over the kor and 100-fold selectivity for the mor over the dor. relative to naltrexone, 6β-naltrexol has about half the affinity for the mor. in contrast to naltrexone, 6β-naltrexol is a neutral antagonist of the mor (as opposed to an inverse agonist) and can antagonize the actions of both agonists and inverse agonists at the receptor. 6β-naltrexol is said to have very limited capacity to cross the blood–brain barrier. however, 6β-naltrexol is still able to cross into the brain and produce central opioid receptor antagonism at sufficient levels. in animal studies, 6β-naltrexol showed about 10-fold separation in potency between peripheral and central opioid antagonism, whereas naltrexone showed no separation. because it is a mor neutral antagonist and hence does not reduce basal mor signaling, 6β-naltrexol shows much lower potential for producing opioid withdrawal symptoms than naltrexone at doses achieving similar central opioid blockade in animal studies. due to the very high levels of 6β-naltrexol that occur during naltrexone therapy, 6β-naltrexol may contribute to the central opioid receptor antagonism of naltrexone.