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Systematic (IUPAC) name
2-(3,4-dichlorophenyl)- N-methyl- N-[(5R,7S,8S)- 7-pyrrolidin-1-yl- 1-oxaspiro[4.5]decan-8-yl] acetamide
Clinical data
Legal status
Routes N/A
CAS number 87151-85-7 YesY
ATC code None
PubChem CID 55652
IUPHAR ligand 1653
Chemical data
Formula C22H30Cl2N2O2 
Mol. mass 425.392 g/mol
 N (what is this?)  (verify)

Spiradoline (U-62066) is a drug which acts as a highly selective κ-opioid agonist.[1] It has analgesic,[2] diuretic[3] and antitussive effects,[4] and produces subjective effects in animals similar to those of ketocyclazocine and allylnormetazocine.[5] The main effect in humans is sedation, along with analgesic and diuretic effects, but significant side effects such as dysphoria and hallucinations have stopped it from being used clinically.[6] Kappa-agonists have been shown to react negatively with the mu receptor[citation needed], instead of having an assumed synergy since they are both opioid receptors, such as with the mu (μ) receptors and delta (δ) receptors (which both mediate pain-relief, euphoria and overall potency of opioid effects).


Spiradoline synthesis: Lester J. Kaplan, The Upjohn Company, U.S. Patent 4,438,130 (1984).

The 3-membered cationic intermediate in parenthese is an aziridine, p-TSA is same as TsOH. DBN is acronym for 1,5-Diazabicyclo(4.3.0)non-5-ene.

Spiradoline synthesis: Lester J. Kaplan, Moses W. McMillan; The Upjohn Company, U.S. Patent 4,588,591 (1986).

Alternatively, according to scheme two the 2-oxaspiro[4.5]dec-7-ene intermediate can be made by D.A. addition of 2-Methylenebutyrolactone to 1,3-Butadiene followed by reduction and intramolecular ring closure.

2-oxaspiro[4.5]dec-7-ene intermediate: Lester J. Kaplan, Moses W. McMillan; The Upjohn Company, U.S. Patent 4,588,591 (1986).

See also[edit]


  1. ^ Vonvoigtlander PF, Lewis RA. Analgesic and mechanistic evaluation of spiradoline, a potent kappa opioid. Journal of Pharmacology and Experimental Therapeutics. 1988 Jul;246(1):259-62. PMID 2839665
  2. ^ Kunihara M, Ohyama M, Nakano M, Hayashi S. Analgesic activity of spiradoline mesylate (U-62,066E), a kappa opioid agonist in mice. Life Sciences. 1989;45(13):1191-8. PMID 2796604
  3. ^ Yamada K, Imai M, Yoshida S. Mechanism of diuretic action of U-62,066E, a kappa opioid receptor agonist. European Journal of Pharmacology. 1989 Jan 31;160(2):229-37. doi:10.1016/0014-2999(89)90495-0 PMID 2547626
  4. ^ Kamei J, Tanihara H, Kasuya Y. Antitussive effects of two specific kappa-opioid agonists, U-50,488H and U-62,066E, in rats. European Journal of Pharmacology. 1990 Oct 9;187(2):281-6. PMID 2272363
  5. ^ Holtzman SG. Further characterization of the discriminative stimulus effects of spiradoline. Pharmacology, Biochemistry and Behaviour. 2000 Jul;66(3):517-22. PMID 10899364
  6. ^ Wadenberg ML. A review of the properties of spiradoline: a potent and selective kappa-opioid receptor agonist. CNS Drug Reviews. 2003 Summer;9(2):187-98. PMID 12847558
  7. ^ Halfpenny, Paul R. (1990). "Highly selective .kappa.-opioid analgesics. 3. Synthesis and structure-activity relationships of novel N-[2-(1-pyrrolidinyl)-4- or -5-substituted cyclohexyl]arylacetamide derivatives". Journal of Medicinal Chemistry 33 (1): 286–291. doi:10.1021/jm00163a047.  edit