 | |
| Clinical data | |
|---|---|
| Other names | 6beta-Naltrexol; 6β-Hydroxynaltrexone; AIKO-150; 17-(Cyclopropylmethyl)-4,5α-epoxymorphinan-3,6α,14-triol |
| Drug class | Opioid antagonist |
| Pharmacokinetic data | |
| Eliminationhalf-life | 12–18 hours[1] |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| UNII | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.230.713 |
| Chemical and physical data | |
| Formula | C20H25NO4 |
| Molar mass | 343.423 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
6β-Naltrexol, or6β-hydroxynaltrexone (developmental code nameAIKO-150), is aperipherally-selectiveopioid receptor antagonist related tonaltrexone.[2][3] It is a majoractive metabolite of naltrexone formed byhepatic dihydrodiol dehydrogenaseenzymes.[2][3] With naltrexone therapy, 6β-naltrexol is present at approximately 10- to 30-fold higher concentrations than naltrexone atsteady state due to extensivefirst-pass metabolism of naltrexone into 6β-naltrexol.[4] In addition to being an active metabolite of naltrexone, 6β-naltrexol was itself studied for the treatment ofopioid-induced constipation.[2][5][6] It was found to be effective and well-tolerated, and did not precipitateopioid withdrawal symptoms or interfere withopioidpain relief, but development was not further pursued.[2][5][6]
6β-Naltrexol binds to theopioid receptors withaffinity (Ki) values of 2.12 nM for theμ-opioid receptor (MOR), 7.24 nM for theκ-opioid receptor (KOR), and 213 nM for theδ-opioid receptor (DOR).[5] Hence, 6β-naltrexol shows 3.5-foldselectivity for the MOR over the KOR and 100-fold selectivity for the MOR over the DOR.[5] Relative to naltrexone, 6β-naltrexol has about half the affinity for the MOR.[1] In contrast to naltrexone, 6β-naltrexol is aneutral antagonist of the MOR (as opposed to aninverse agonist) and can antagonize the actions of bothagonists and inverse agonists at the receptor.[7]
6β-Naltrexol is said to have very limited capacity to cross theblood–brain barrier.[8] However, 6β-naltrexol is still able to cross into the brain and produce central opioid receptor antagonism at sufficient levels.[5] In animal studies, 6β-naltrexol showed about 10-fold separation inpotency between peripheral and central opioid antagonism, whereas naltrexone showed no separation.[5] Because it is a MOR neutral antagonist and hence does not reduce basal MOR signaling, 6β-naltrexol shows much lower potential for producingopioid withdrawal symptoms than naltrexone at doses achieving similar central opioid blockade in animal studies.[5][7] 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.[9]
 | Thisdrug article relating to thegastrointestinal system is astub. You can help Wikipedia byexpanding it. |