Β-Funaltrexamine Explained

Drug Name:	β-Funaltrexamine
Width:	175px
Cas Number:	72782-05-9
Pubchem:	5311018
Chemspiderid:	4470557
Unii:	9YX958J3X9
Kegg:	C18127
Chebi:	81527
Chembl:	473136
Synonyms:	Funaltrexamine; β-Funaltrexamine; Beta-Funaltrexamine; β-FNA; Beta-FNA
Iupac Name:	methyl (E)-4-(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ylamino]-4-oxobut-2-enoate or Methyl (2E)-4--4-oxobut-2-enoate
C:	25
H:	30
N:	2
O:	6
Smiles:	COC(=O)/C=C/C(=O)N[C@@H]1CC[C@]2([C@H]3CC4=C5[C@]2([C@H]1OC5=C(C=C4)O)CCN3CC6CC6)O
Stdinchi:	1S/C25H30N2O6/c1-32-20(30)7-6-19(29)26-16-8-9-25(31)18-12-15-4-5-17(28)22-21(15)24(25,23(16)33-22)10-11-27(18)13-14-2-3-14/h4-7,14,16,18,23,28,31H,2-3,8-13H2,1H3,(H,26,29)/b7-6+/t16-,18-,23+,24+,25-/m1/s1
Stdinchikey:	PQKHESYTSKMWFP-WZJCLRDWSA-N

β-Funaltrexamine (β-FNA) is an irreversible (covalently bonding) opioid antagonist that was used to create the first crystal structure of the μ-opioid receptor (MOR).^[1] It is selective for antagonism of the MOR over the δ-opioid receptor (DOR) and κ-opioid receptor (KOR).^[2] Chemically, it is a naltrexone derivative with a methyl-fumaramide group in the 6-position. In addition to its MOR irreversible antagonism, β-FNA is a reversible agonist of the κ-opioid receptor (KOR) and produces KOR-mediated analgesic effects in animals.^[3] ^[4] This has limited its usefulness and contributed to the development of methocinnamox as a more selective functionally irreversible antagonist of the MOR with no significant opioid agonistic actions.

Notes and References

Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S . 6 . Crystal structure of the µ-opioid receptor bound to a morphinan antagonist . Nature . 485 . 7398 . 321–6 . March 2012 . 22437502 . 3523197 . 10.1038/nature10954 . 2012Natur.485..321M .
Ward SJ, Portoghese PS, Takemori AE . Pharmacological profiles of beta-funaltrexamine (beta-FNA) and beta-chlornaltrexamine (beta-CNA) on the mouse vas deferens preparation . Eur J Pharmacol . 80 . 4 . 377–384 . June 1982 . 6286325 . 10.1016/0014-2999(82)90083-8 .
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 . J Pharmacol Exp Ther . 294 . 3 . 933–940 . September 2000 . 10945843 .
Qi JA, Heyman JS, Sheldon RJ, Koslo RJ, Porreca F . Mu antagonist and kappa agonist properties of beta-funaltrexamine (beta-FNA) in vivo: long-lasting spinal analgesia in mice . J Pharmacol Exp Ther . 252 . 3 . 1006–1011 . March 1990 . 2156986 .