U-69,593

{{Short description|Chemical compound}}

{{Drugbox

| IUPAC_name = N-methyl-2-phenyl-N-[(5R,7S,8S)-7-(pyrrolidin-1-yl)-1-oxaspiro[4.5]dec-8-yl]acetamide

| image = U-69,593 structure.svg

| tradename =

| pregnancy_category =

| legal_status =

| routes_of_administration =

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number = 96744-75-1

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = J5S4K6TKTG

| ATC_prefix = none

| ATC_suffix =

| PubChem = 105104

| IUPHAR_ligand = 1655

| ChemSpiderID = 94828

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 73357

| ChEMBL = 440765

| C=22 | H=32 | N=2 | O=2

| smiles = O=C(N([C@H]3CC[C@]1(OCCC1)C[C@@H]3N2CCCC2)C)Cc4ccccc4

}}

U-69,593 is a drug which acts as a potent and selective κ₁-opioid receptor agonist.{{cite journal |vauthors=La Regina A, Petrillo P, Sbacchi M, Tavani A | title = Interaction of U-69,593 with mu-, alpha- and kappa-opioid binding sites and its analgesic and intestinal effects in rats | journal = Life Sciences | volume = 42 | issue = 3 | pages = 293–301 | year = 1988 | pmid = 2826959 | doi = 10.1016/0024-3205(88)90638-8}}{{cite journal | author = Frey HH | title = Effect of mu- and kappa-opioid agonists on the electroconvulsive seizure threshold in mice and antagonism by naloxone and MR 2266 | journal = Pharmacology & Toxicology | volume = 62 | issue = 3 | pages = 150–4 |date=March 1988 | pmid = 2836842 | doi = 10.1111/j.1600-0773.1988.tb01863.x}}{{cite journal |vauthors=Zukin RS, Eghbali M, Olive D, Unterwald EM, Tempel A | title = Characterization and visualization of rat and guinea pig brain kappa opioid receptors: evidence for kappa 1 and kappa 2 opioid receptors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 11 | pages = 4061–5 |date=June 1988 | pmid = 2836869 | pmc = 280361 | doi = 10.1073/pnas.85.11.4061| bibcode = 1988PNAS...85.4061Z | doi-access = free }} In animal studies it has been shown to produce antinociception,{{cite journal |vauthors=Millan MJ, Członkowski A, Lipkowski A, Herz A | title = Kappa-opioid receptor-mediated antinociception in the rat. II. Supraspinal in addition to spinal sites of action | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 251 | issue = 1 | pages = 342–50 |date=October 1989 | pmid = 2571723 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2571723}}{{cite journal |vauthors=France CP, Medzihradsky F, Woods JH | title = Comparison of kappa opioids in rhesus monkeys: behavioral effects and receptor binding affinities | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 268 | issue = 1 | pages = 47–58 |date=January 1994 | pmid = 8301589 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8301589}} anti-inflammation,{{cite journal |vauthors=Binder W, Machelska H, Mousa S, etal | title = Analgesic and antiinflammatory effects of two novel kappa-opioid peptides | journal = Anesthesiology | volume = 94 | issue = 6 | pages = 1034–44 |date=June 2001 | pmid = 11465595 | doi = 10.1097/00000542-200106000-00018| s2cid = 46531607 | url = https://dx.doi.org/10.1097/00000542-200106000-00018}} anxiolysis (at low doses),{{cite journal |vauthors=Privette TH, Terrian DM | title = Kappa opioid agonists produce anxiolytic-like behavior on the elevated plus-maze | journal = Psychopharmacology | volume = 118 | issue = 4 | pages = 444–50 |date=April 1995 | pmid = 7568631 | doi = 10.1007/BF02245945| s2cid = 21326960 }}{{cite journal |vauthors=Wall PM, Messier C | title = U-69,593 microinjection in the infralimbic cortex reduces anxiety and enhances spontaneous alternation memory in mice | journal = Brain Research | volume = 856 | issue = 1–2 | pages = 259–80 |date=February 2000 | pmid = 10677636 | doi = 10.1016/S0006-8993(99)01990-3| s2cid = 11630212 }}{{cite journal |vauthors=Wall PM, Messier C | title = Concurrent modulation of anxiety and memory | journal = Behavioural Brain Research | volume = 109 | issue = 2 | pages = 229–41 |date=May 2000 | pmid = 10762693 | doi = 10.1016/S0166-4328(99)00177-1| s2cid = 42974528 }} respiratory depression, and diuresis,{{cite journal |vauthors=Soulard CD, Guerif S, Payne A, Dahl SG | title = Differential effects of fedotozine compared to other kappa agonists on diuresis in rats | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 279 | issue = 3 | pages = 1379–85 |date=December 1996 | pmid = 8968362 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8968362}} while having little effect on gastrointestinal motility. It also inhibits the peripheral, though not central secretion of oxytocin and vasopressin in rats.{{cite journal |vauthors=Van de Heijning BJ, Koekkoek-Van den Herik I, Van Wimersma Greidanus TB | title = The opioid receptor subtypes mu and kappa, but not delta, are involved in the control of the vasopressin and oxytocin release in the rat | journal = European Journal of Pharmacology | volume = 209 | issue = 3 | pages = 199–206 |date=December 1991 | pmid = 1665795 | doi = 10.1016/0014-2999(91)90170-U}}{{cite journal |vauthors=Melis MR, Stancampiano R, Gessa GL, Argiolas A | title = Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning: site of action in the brain | journal = Neuropsychopharmacology | volume = 6 | issue = 1 | pages = 17–21 |date=January 1992 | pmid = 1315136 }}