Methocinnamox

Not to be confused with Methoclocinnamox.
Methocinnamox
Clinical data
Other namesMCAM; M-CAM
Routes of
administration		Intravenous, subcutaneous injection[1]
Drug classOpioid receptor antagonist[1]
Identifiers
  • (E)-N-[(4R,4aS,7aR,12bR)-3-(Cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl]-3-(4-methylphenyl)prop-2-enamide
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC30H32N2O4
Molar mass484.596 g·mol−1
3D model (JSmol)
  • CC1=CC=C(C=C1)/C=C/C(=O)N[C@@]23CCC(=O)[C@H]4[C@@]25CCN([C@@H]3CC6=C5C(=C(C=C6)O)O4)CC7CC7
  • InChI=1S/C30H32N2O4/c1-18-2-4-19(5-3-18)8-11-25(35)31-30-13-12-23(34)28-29(30)14-15-32(17-20-6-7-20)24(30)16-21-9-10-22(33)27(36-28)26(21)29/h2-5,8-11,20,24,28,33H,6-7,12-17H2,1H3,(H,31,35)/b11-8+/t24-,28+,29+,30-/m1/s1
  • Key:PJOHVEQSYPOERL-SHEAVXILSA-N

Methocinnamox (MCAM) is an opioid receptor antagonist.[1][2] It is a pseudo-irreversible non-competitive antagonist of the μ-opioid receptor and a competitive antagonist of the κ- and δ-opioid receptors.[1][2] The drug has a very long duration of action of up to months with a single dose due to its pseudo-irreversibility.[1][2] It is administered in animals by intravenous or subcutaneous injection.[1]

It was first described in the scientific literature in 2000.[1][3][4] It has not been studied in humans as of 2022.[1] There is interest in methocinnamox in the potential treatment of opioid use disorder and opioid overdose due to its much longer-lasting and insurmountable effects relative to other opioid antagonists like naloxone and naltrexone.[1][2] Clinical trials of the drug are expected.[3][5]

Methocinnamox should not be confused with methoclocinnamox (MCCAM), which is a closely related but structurally different compound (chlorine instead of methyl on one of the benzene rings).[6][7] The drug was derived via structural modification of buprenorphine.[8]

  1. ^ a b c d e f g h i Jordan CG, Kennalley AL, Roberts AL, Nemes KM, Dolma T, Piper BJ (April 2022). "The Potential of Methocinnamox as a Future Treatment for Opioid Use Disorder: A Narrative Review". Pharmacy. 10 (3): 48. doi:10.3390/pharmacy10030048. PMC 9149874. PMID 35645327.
  2. ^ a b c d Maguire DR, France CP (March 2023). "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. doi:10.1002/jeab.831. PMC 10281830. PMID 36759567.
  3. ^ a b Cite error: The named reference Moss2020 was invoked but never defined (see the help page).
  4. ^ Broadbear JH, Sumpter TL, Burke TF, Husbands SM, Lewis JW, Woods JH, et al. (September 2000). "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. PMID 10945843.
  5. ^ Alvarez-Hernandez J (7 March 2023). "UT Health San Antonio Professor France leads novel drug discovery research". UT Health San Antonio. Retrieved 9 August 2024. Charles P. France, PhD, the Robert A. Welch Distinguished University Chair in Chemistry, professor of pharmacology and professor of psychiatry in the Joe R. and Teresa Lozano Long School of Medicine at The University of Texas Health Science Center at San Antonio (UT Health San Antonio), recently received a $4.12 million award from the U.S. National Institutes of Health (NIH) to investigate innovative drug development research of the compound methocinnamox (MCAM) to help combat the opioid epidemic. [...] This NIH funding mechanism, specifically UG3/UH3, has one precise objective to advance the discovery into the clinical setting. "We want to get this into the clinic," France said. [...] "Under the best of conditions, we hope to have this compound into a phase one clinical trial sometime in 2024."
  6. ^ Neilan CL (8 August 2019). In vitro and in vivo characterisation of buprenorphine and other long-lasting opioids (Thesis). Loughborough University. Retrieved 9 August 2024.
  7. ^ "Methoclocinnamox". PubChem. U.S. National Library of Medicine. Retrieved 9 August 2024.
  8. ^ Gerak LR, Maguire DR, France CP (2019). "Behavioral Pharmacology of Drugs Acting at Mu Opioid Receptors". Substance Use Disorders. Handbook of Experimental Pharmacology. Vol. 258. Cham: Springer International Publishing. pp. 127–145. doi:10.1007/164_2019_265. ISBN 978-3-030-33678-3. PMID 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).