U-69,593 Explained

U-69,593 is a drug which acts as a potent and selective κ₁-opioid receptor agonist.^{[1] [2] [3]} In animal studies it has been shown to produce antinociception,^{[1] [4] [5]} anti-inflammation,^[6] anxiolysis (at low doses),^{[7] [8] [9]} respiratory depression,^[5] and diuresis,^[10] while having little effect on gastrointestinal motility.^[1] It also inhibits the peripheral, though not central secretion of oxytocin and vasopressin in rats.^{[11] [12]}

See also

• U-50,488
• The dichloro analog is called spiradoline.

Notes and References

1. La Regina A, Petrillo P, Sbacchi M, Tavani A . Interaction of U-69,593 with mu-, alpha- and kappa-opioid binding sites and its analgesic and intestinal effects in rats . Life Sciences . 42 . 3 . 293–301 . 1988 . 2826959 . 10.1016/0024-3205(88)90638-8.
2. Frey HH . Effect of mu- and kappa-opioid agonists on the electroconvulsive seizure threshold in mice and antagonism by naloxone and MR 2266 . Pharmacology & Toxicology . 62 . 3 . 150–4 . March 1988 . 2836842 . 10.1111/j.1600-0773.1988.tb01863.x.
3. Zukin RS, Eghbali M, Olive D, Unterwald EM, Tempel A . Characterization and visualization of rat and guinea pig brain kappa opioid receptors: evidence for kappa 1 and kappa 2 opioid receptors . Proceedings of the National Academy of Sciences of the United States of America . 85 . 11 . 4061–5 . June 1988 . 2836869 . 280361 . 10.1073/pnas.85.11.4061. 1988PNAS...85.4061Z . free .
4. Millan MJ, Członkowski A, Lipkowski A, Herz A . Kappa-opioid receptor-mediated antinociception in the rat. II. Supraspinal in addition to spinal sites of action . The Journal of Pharmacology and Experimental Therapeutics . 251 . 1 . 342–50 . October 1989 . 2571723 .
5. France CP, Medzihradsky F, Woods JH . Comparison of kappa opioids in rhesus monkeys: behavioral effects and receptor binding affinities . The Journal of Pharmacology and Experimental Therapeutics . 268 . 1 . 47–58 . January 1994 . 8301589 .
6. Binder W, Machelska H, Mousa S, etal . Analgesic and antiinflammatory effects of two novel kappa-opioid peptides . Anesthesiology . 94 . 6 . 1034–44 . June 2001 . 11465595 . 10.1097/00000542-200106000-00018. 46531607 .
7. Privette TH, Terrian DM . Kappa opioid agonists produce anxiolytic-like behavior on the elevated plus-maze . Psychopharmacology . 118 . 4 . 444–50 . April 1995 . 7568631 . 10.1007/BF02245945. 21326960 .
8. Wall PM, Messier C . U-69,593 microinjection in the infralimbic cortex reduces anxiety and enhances spontaneous alternation memory in mice . Brain Research . 856 . 1–2 . 259–80 . February 2000 . 10677636 . 10.1016/S0006-8993(99)01990-3. 11630212 .
9. Wall PM, Messier C . Concurrent modulation of anxiety and memory . Behavioural Brain Research . 109 . 2 . 229–41 . May 2000 . 10762693 . 10.1016/S0166-4328(99)00177-1. 42974528 .
10. Soulard CD, Guerif S, Payne A, Dahl SG . Differential effects of fedotozine compared to other kappa agonists on diuresis in rats . The Journal of Pharmacology and Experimental Therapeutics . 279 . 3 . 1379–85 . December 1996 . 8968362 .
11. Van de Heijning BJ, Koekkoek-Van den Herik I, Van Wimersma Greidanus TB . The opioid receptor subtypes mu and kappa, but not delta, are involved in the control of the vasopressin and oxytocin release in the rat . European Journal of Pharmacology . 209 . 3 . 199–206 . December 1991 . 1665795 . 10.1016/0014-2999(91)90170-U.
12. Melis MR, Stancampiano R, Gessa GL, Argiolas A . Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning: site of action in the brain . Neuropsychopharmacology . 6 . 1 . 17–21 . January 1992 . 1315136 .