Clocinnamox Explained
| Width: | 250px |
| Cas Number: | 117332-69-1 |
| Pubchem: | 6540640 |
| Chemspiderid: | 5022878 |
| Chembl: | 386492 |
| Synonyms: | C-CAM; CCAM; NIH-10443 |
| Iupac Name: | (E)-N-[(4''R'',4a''S'',7a''R'',12b''R'')-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1''H''-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl]-3-(4-chlorophenyl)prop-2-enamide
or
(2E)-3-(4-chlorophenyl)-N-[(5α)-17-(cyclopropylmethyl)-3-hydroxy-6-oxo-4,5-epoxymorphinan-14-yl]acrylamide |
| C: | 29 |
| H: | 29 |
| Cl: | 1 |
| N: | 2 |
| O: | 4 |
| Smiles: | C1CC1CN2CC[C@]34[C@@H]5C(=O)CC[C@]3([C@H]2CC6=C4C(=C(C=C6)O)O5)NC(=O)/C=C/C7=CC=C(C=C7)Cl |
| Stdinchi: | 1S/C29H29ClN2O4/c30-20-7-3-17(4-8-20)5-10-24(35)31-29-12-11-22(34)27-28(29)13-14-32(16-18-1-2-18)23(29)15-19-6-9-21(33)26(36-27)25(19)28/h3-10,18,23,27,33H,1-2,11-16H2,(H,31,35)/b10-5+/t23-,27+,28+,29-/m1/s1 |
| Stdinchikey: | RAURUSFBVQLAPW-DNIKMYEQSA-N |
Clocinnamox (CCAM or C-CAM; developmental code name NIH-10443) is a selective and irreversible antagonist of the μ-opioid receptor.[1] [2] Closely related compounds include methocinnamox (MCAM) and methoclocinnamox (MCCAM).[3] [4] [5] They were derived via structural modification of buprenorphine.[6] Clocinnamox was first described in the scientific literature by 1992.[7]
Notes and References
- Book: Woods JH, Lewis JW, Winger G, Butelman E, Broadbear J, Zernig G . National Institute on Drug Abuse . Methoclocinnamox: A μ Partial Agonist With Pharmacotherapeutic Potential for Heroin Abuse . NIDA Research Monograph . National Institute on Drug Abuse . DHEW publication . v. 147 . 1995 . https://books.google.com/books?id=MtPF6qZ9l9wC&pg=PA195 . 9 August 2024 . 195–219.
- Filho CB, Del Fabbro L, de Gomes MG, Goes AT, Souza LC, Boeira SP, Jesse CR . Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test . European Journal of Pharmacology . 698 . 1–3 . 286–291 . January 2013 . 23178563 . 10.1016/j.ejphar.2012.11.003 .
- Jordan CG, Kennalley AL, Roberts AL, Nemes KM, Dolma T, Piper BJ . The Potential of Methocinnamox as a Future Treatment for Opioid Use Disorder: A Narrative Review . Pharmacy . 10 . 3 . 48 . April 2022 . 35645327 . 9149874 . 10.3390/pharmacy10030048 . free .
- Maguire DR, France CP . Behavioral pharmacology of methocinnamox: A potential new treatment for opioid overdose and opioid use disorder . Journal of the Experimental Analysis of Behavior . 119 . 2 . 392–406 . March 2023 . 36759567 . 10281830 . 10.1002/jeab.831 .
- Broadbear JH, Sumpter TL, Burke TF, Husbands SM, Lewis JW, Woods JH, Traynor JR . Methocinnamox is a potent, long-lasting, and selective antagonist of morphine-mediated antinociception in the mouse: comparison with clocinnamox, beta-funaltrexamine, and beta-chlornaltrexamine . The Journal of Pharmacology and Experimental Therapeutics . 294 . 3 . 933–940 . September 2000 . 10945843 .
- Book: Gerak LR, Maguire DR, France CP . Substance Use Disorders . Behavioral Pharmacology of Drugs Acting at Mu Opioid Receptors . Handbook of Experimental Pharmacology . Springer International Publishing . Cham . 258 . 2019 . 978-3-030-33678-3 . 10.1007/164_2019_265 . 127–145 . 31451969 . Given the advantages of buprenorphine as a treatment for opioid use disorder, additional compounds related to buprenorphine were synthesized in an attempt to reduce its adverse effects (Broadbear et al. 2000). These efforts resulted in the discovery of the mu opioid receptor antagonist methocinnamox (MCAM). Like buprenorphine, MCAM binds pseudoirreversibly to mu opioid receptors; however, it does not appear to produce agonist effects at mu opioid receptors under any conditions. Instead, MCAM produces long-lasting antagonism at mu opioid receptors, as evidenced by attenuation of the antinociceptive effects of morphine in rodents, with the morphine dose-effect curve shifted up to hundredfold rightward (Peckham et al. 2005) and antagonist effects evident for at least 2 days after administration (Broadbear et al. 2000)..
- Comer SD, Burke TF, Lewis JW, Woods JH . Clocinnamox: a novel, systemically-active, irreversible opioid antagonist . The Journal of Pharmacology and Experimental Therapeutics . 262 . 3 . 1051–1056 . September 1992 . 1326622 .
