Samidorphan
 | |
| Systematic (IUPAC) name | |
|---|---|
|
17-(Cyclopropylmethyl)-4,14-dihydroxy-6-oxomorphinan-3-carboxamide | |
| Pharmacokinetic data | |
| Biological half-life | 7–9 hours[1] |
| Identifiers | |
| CAS Number |
852626-89-2  |
| PubChem | CID 11667832 |
| ChemSpider | 23259667 |
| UNII |
7W2581Z5L8 |
| KEGG |
D10162 |
| Synonyms | ALKS-33, RDC-0313 |
| Chemical data | |
| Formula | C21H26N2O4 |
| Molar mass | 370.441 g/mol |
| |
| |
Samidorphan (INN, USAN) (developmental code names ALKS-33, RDC-0313), also known as 3-carboxamido-4-hydroxynaltrexone, is an opioid antagonist that selectively blocks the μ-opioid receptor, without blocking the δ-opioid or κ-opioid receptors. It has been investigated for the treatment of alcoholism and cocaine addiction by its developer, Alkermes,[2][3] showing similar efficacy to naltrexone but possibly with reduced side effects.
However, it has attracted much more attention as part of the combination product ALKS-5461, where samidorphan is combined with the mixed μ-opioid agonist and κ-opioid antagonist opioid modulator buprenorphine, as an antidepressant. Buprenorphine has shown antidepressant effects in some human studies, thought to be because of its antagonist effects at the κ-opioid receptor, but has not been further developed for this application because of its μ-opioid agonist effects and consequent abuse potential. By combining buprenorphine with samidorphan to block the μ-opioid agonist effects, the combination acts more like a selective κ-opioid antagonist, and produces only antidepressant effects, without typical μ-opioid effects being evident.[4][5]
Samidorphan is also being studied in combination with olanzapine, as ALKS-3831, for use in schizophenia.[6] It is hoped it will be effective while resulting in less weight gain. Phase II studies have begun.[7]
See also
References
- ↑ Single- and multiple-dose pharmacokinetics of samidorphan, a novel opioid antagonist, in healthy volunteers Clin Ther. 2015 Feb 1;37(2):338-48. doi: 10.1016/j.clinthera.2014.10.001. Epub 2014 Oct 29.
- ↑ Hillemacher, T.; Heberlein, A.; Muschler, M. A.; Bleich, S.; Frieling, H. (2011). "Opioid modulators for alcohol dependence". Expert Opinion on Investigational Drugs 20 (8): 1073–1086. doi:10.1517/13543784.2011.592139. PMID 21651459.
- ↑ ALK33BUP-101: Safety and Pharmacodynamic Effects of ALKS 33-BUP Administered Alone and When Co-administered With Cocaine
- ↑ ALKS 5461 drug found to reduce depressive symptoms in Phase 1/2 study
- ↑ Investigational ALKS 5461 Channels ‘Opium Cure’ for Depression
- ↑ "Will Alkermes' Antipsychotic ALKS-3831 Become Another Tredaptive?". Forbes. Jan 15, 2013.
- ↑ "A Study of ALKS 3831 in Subjects With Schizophrenia and Alcohol Use Disorder".