Samidorphan

Samidorphan

Clinical data
Routes of administration	Oral
Pharmacokinetic data
Biological half-life	7–9 hours
Identifiers
IUPAC name 17-(Cyclopropylmethyl)-4,14-dihydroxy-6-oxomorphinan-3-carboxamide
Synonyms	ALKS-33, RDC-0313; 3-Carboxamido-4-hydroxynaltrexone
CAS Number	852626-89-2 Y
PubChem CID	11667832
ChemSpider	23259667
UNII	7W2581Z5L8
KEGG	D10162 Y
Chemical and physical data
Formula	C21H26N2O4
Molar mass	370.441 g/mol
3D model (Jmol)	Interactive image
SMILES c1cc(c(c2c1C[C@@H]3[C@]4([C@]2(CCN3CC5CC5)CC(=O)CC4)O)O)C(=O)N
InChI InChI=1S/C21H26N2O4/c22-19(26)15-4-3-13-9-16-21(27)6-5-14(24)10-20(21,17(13)18(15)25)7-8-23(16)11-12-1-2-12/h3-4,12,16,25,27H,1-2,5-11H2,(H2,22,26)/t16-,20-,21-/m1/s1 Key:RYIDHLJADOKWFM-MAODMQOUSA-N

Samidorphan (INN, USAN) (developmental code names ALKS-33, RDC-0313), also known as 3-carboxamido-4-hydroxynaltrexone, is an opioid antagonist that preferentially acts as an antagonist of the μ-opioid receptor (MOR). It is under development by Alkermes for the treatment of major depressive disorder and possibly other psychiatric conditions.

Samidorphan has been investigated for the treatment of alcoholism and cocaine addiction by its developer, Alkermes, 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 MOR weak partial agonist and κ-opioid receptor (KOR) antagonist buprenorphine, as an antidepressant. Buprenorphine has shown antidepressant effects in some human studies, thought to be because of its antagonist effects at the KOR, but has not been further developed for this application because of its MOR agonist effects and consequent abuse potential. By combining buprenorphine with samidorphan to block the MOR agonist effects, the combination acts more like a selective KOR antagonist, and produces only antidepressant effects, without typical MOR effects such as euphoria or substance dependence being evident.