Xorphanol

Xorphanol
Clinical data
ATC code	none;
Identifiers
	IUPAC name N-(Cyclobutylmethyl)-8β-methyl-6-methylenemorphinan-3-ol;
CAS Number	77287-89-9 ;
PubChem CID	5488631;
ChemSpider	20121496 ;
UNII	L415991P58;
Chemical and physical data
Formula	C23H31NO
Molar mass	337.498 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@H]1CC(=C)C[C@@]23[C@@H]1[C@@H](CC4=C2C=C(C=C4)O)N(CC3)CC5CCC5;
	InChI InChI=1S/C23H31NO/c1-15-10-16(2)22-21-11-18-6-7-19(25)12-20(18)23(22,13-15)8-9-24(21)14-17-4-3-5-17/h6-7,12,16-17,21-22,25H,1,3-5,8-11,13-14H2,2H3/t16-,21+,22-,23+/m0/s1 ; Key:AZJPPZHRNFQRRE-AZIXLERZSA-N ;
	(what is this?) (verify)

Xorphanol (developmental code name TR-5379) is an opioid analgesic of the morphinan family that was never marketed. It is a mixed agonist–antagonist of the μ- and κ-opioid receptors^[1]^[2]^[3] and produces potent analgesic effects whilst originally being purported to possess a minimal potential for dependence or abuse.^[4]^[5]^[6] The drug is a high-efficacy partial agonist/near-full agonist of the κ-opioid receptor (K_i = 0.4 nM; EC₅₀ = 3.3 nM; E_max = 84%).^[7]

Side effects in animal studies were relatively mild, with only sedation and nausea being prominent, although it also produced convulsions at the highest dose tested.^[8] However human trials revealed additional side effects such as headaches and euphoria, and this was the subject of a lawsuit between the drug's inventors and the company to which they had licensed the marketing rights, which claimed that these side effects had not been revealed to them during the license negotiations.^[9] This dispute resulted in the drug never being marketed commercially.

References

^ Deborah L. Colbern; Willem Hendrik Gispen; New York Academy of Sciences (1 January 1988). Neural Mechanisms and Biological Significance of Grooming Behavior. New York Academy of Sciences. ISBN 978-0-89766-441-7.
^ Gmerek, Debra E.; Cowan, A. (1988). "Role of Opioid Receptors in Bombesin-induced Grooming". Annals of the New York Academy of Sciences. 525 (1 Neural Mechan): 291–300. doi:10.1111/j.1749-6632.1988.tb38614.x. ISSN 0077-8923.
^ Cowan A, Zhu XZ, Mosberg HI, Porreca F (1986). "Central infusion of rats with agents selective for different types of opioid receptor". NIDA Res. Monogr. 67: 132–7. PMID 3018570.
^ Polazzi, JO; Kotick, MP; Howes, JF; Bousquet, AR (1981). "Analgesic narcotic antagonists. 9. 6-Methylene-8 beta-alkyl-N-(cycloalkylmethyl)-3-hydroxy- or -methoxymorphinans". Journal of Medicinal Chemistry. 24 (12): 1516–8. doi:10.1021/jm00144a029. PMID 6796691.
^ McCarthy, PS; Howlett, GJ (1984). "Physical dependence induced by opiate partial agonists in the rat". Neuropeptides. 5 (1–3): 11–4. doi:10.1016/0143-4179(84)90014-3. PMID 6152317.
^ Howes, JF; Villarreal, JE; Harris, LS; Essigmann, EM; Cowan, A (1985). "Xorphanol". Drug and Alcohol Dependence. 14 (3–4): 373–80. doi:10.1016/0376-8716(85)90068-7. PMID 4039650.
^ Gharagozlou, Parham; Hashemi, Ezzat; DeLorey, TimothyM; Clark, J David; Lameh, Jelveh (2006). "Pharmacological profiles of opioid ligands at Kappa opioid receptors". BMC Pharmacology. 6 (1): 3. doi:10.1186/1471-2210-6-3. ISSN 1471-2210.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Porter, MC; Hartnagel, RE; Clemens, GR; Kowalski, RL; Bare, JJ; Halliwell, WE; Kitchen, DN (1983). "Preclinical toxicity and teratogenicity studies with the narcotic antagonist analgesic drug TR5379M". Fundamental and applied toxicology : official journal of the Society of Toxicology. 3 (5): 478–82. doi:10.1016/S0272-0590(83)80023-2. PMID 6642105.
^ Maruho Company Ltd v Miles Inc (1993) 13 F.3d 6

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[ColbernGispen1988-1] Deborah L. Colbern; Willem Hendrik Gispen; New York Academy of Sciences (1 January 1988). Neural Mechanisms and Biological Significance of Grooming Behavior. New York Academy of Sciences. ISBN 978-0-89766-441-7.

[GmerekCowan1988-2] Gmerek, Debra E.; Cowan, A. (1988). "Role of Opioid Receptors in Bombesin-induced Grooming". Annals of the New York Academy of Sciences. 525 (1 Neural Mechan): 291–300. doi:10.1111/j.1749-6632.1988.tb38614.x. ISSN 0077-8923.

[pmid3018570-3] Cowan A, Zhu XZ, Mosberg HI, Porreca F (1986). "Central infusion of rats with agents selective for different types of opioid receptor". NIDA Res. Monogr. 67: 132–7. PMID 3018570.

[4] Polazzi, JO; Kotick, MP; Howes, JF; Bousquet, AR (1981). "Analgesic narcotic antagonists. 9. 6-Methylene-8 beta-alkyl-N-(cycloalkylmethyl)-3-hydroxy- or -methoxymorphinans". Journal of Medicinal Chemistry. 24 (12): 1516–8. doi:10.1021/jm00144a029. PMID 6796691.

[5] McCarthy, PS; Howlett, GJ (1984). "Physical dependence induced by opiate partial agonists in the rat". Neuropeptides. 5 (1–3): 11–4. doi:10.1016/0143-4179(84)90014-3. PMID 6152317.

[6] Howes, JF; Villarreal, JE; Harris, LS; Essigmann, EM; Cowan, A (1985). "Xorphanol". Drug and Alcohol Dependence. 14 (3–4): 373–80. doi:10.1016/0376-8716(85)90068-7. PMID 4039650.

[GharagozlouHashemi2006-7] Gharagozlou, Parham; Hashemi, Ezzat; DeLorey, TimothyM; Clark, J David; Lameh, Jelveh (2006). "Pharmacological profiles of opioid ligands at Kappa opioid receptors". BMC Pharmacology. 6 (1): 3. doi:10.1186/1471-2210-6-3. ISSN 1471-2210.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[8] Porter, MC; Hartnagel, RE; Clemens, GR; Kowalski, RL; Bare, JJ; Halliwell, WE; Kitchen, DN (1983). "Preclinical toxicity and teratogenicity studies with the narcotic antagonist analgesic drug TR5379M". Fundamental and applied toxicology : official journal of the Society of Toxicology. 3 (5): 478–82. doi:10.1016/S0272-0590(83)80023-2. PMID 6642105.

[9] Maruho Company Ltd v Miles Inc (1993) 13 F.3d 6

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See also

References