Spiradoline ( U-62066) is a drug which acts as a highly selective κ-opioid agonist. It has [1 ] analgesic, [2 ] diuretic and [3 ] antitussive effects, and produces subjective effects in animals similar to those of [4 ] ketocyclazocine and allylnormetazocine. The main effect in humans is [5 ] sedation, along with analgesic and diuretic effects, but significant side effects such as dysphoria and hallucinations have stopped it from being used clinically. Kappa-agonists have been shown to react negatively with the [6 ] mu receptor, 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).
Synthesis [ edit ]
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.
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.
See also [ edit ]
References [ edit ]
^ 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
^ 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
^ 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
^ 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
^ Holtzman SG. Further characterization of the discriminative stimulus effects of spiradoline. Pharmacology, Biochemistry and Behaviour. 2000 Jul;66(3):517-22. PMID 10899364
^ 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
5-HT 2AR agonists
5-MeO-2, N, N-TMT
5-MeO-4, N, N-TMT
5- N, N-TMT
Note: The above list contains only
some known MOR agonists, as far too many exist to list here completely. Refer here instead for more.