JNJ-20788560 [9-(8-azabicyclo[3.2.1]oct-3-ylidene)-9H- Xanthene-3- carboxylic acid diethylamide], a selective delta opioid receptor agonist, is a potent and efficacious antihyperalgesic agent that does not produce respiratory depression, pharmacologic tolerance, or physical dependence

Journal of Pharmacology and Experimental Therapeutics

Volumn 329, Issue 1, 2009, Pages 241-251

  Codd, Ellen E ^a   Carson, John R ^a   Colburn, Raymond W ^a   Stone, Dennis J ^a   Besien, Christopher R V ^a   Zhang, Sui Po ^a   Wade, Paul R ^a   Gallantine, Elizabeth L ^b   Meert, Theo F ^b   Molino, Lory ^a   Pullan, Shirley ^b   Razler, Christine M ^a   Dax, Scott L ^a   Flores, Christopher M ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

^b JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,4,4A,5,12,12AALPHA OCTAHYDRO 4AALPHA (3 HYDROXYPHENYL) 2 METHYLQUINOLINO[2,3 G]ISOQUINOLINE; 4 [ALPHA (4 ALLYL 2,5 DIMETHYL 1 PIPERAZINYL) 3 METHOXYBENZYL] N,N DIETHYLBENZAMIDE; 9 [8 AZABICYCLO(3.2.1)OCT 3 YLIDENE] 9H XANTHENE 3 CARBOXYLIC ACID DIETHYLAMIDE; CELECOXIB; DELTA OPIATE RECEPTOR; DELTA OPIATE RECEPTOR AGONIST; ENKEPHALIN[2,5 DEXTRO PENICILLAMINE]; IBUPROFEN; JNJ 20788560; MORPHINE; NARCOTIC ANALGESIC AGENT; UNCLASSIFIED DRUG; ZYMOSAN;

ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINOCICEPTION; ARTICLE; BINDING AFFINITY; BLOOD GAS ANALYSIS; CONTROLLED STUDY; CONVULSION; DIGESTIVE SYSTEM INJURY; DOSE RESPONSE; DRUG DEPENDENCE; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG TOLERANCE; GASTROINTESTINAL DISEASE; GASTROINTESTINAL MOTILITY; HYPERALGESIA; IN VITRO STUDY; MALE; MOUSE; NEUROPATHIC PAIN; NONHUMAN; PRIORITY JOURNAL; RAT; RESPIRATION DEPRESSION;

ALFENTANIL; ANALGESICS, OPIOID; ANIMALS; AZABICYCLO COMPOUNDS; CRICETINAE; DRUG TOLERANCE; GASTROINTESTINAL MOTILITY; GUANOSINE 5'-O-(3-THIOTRIPHOSPHATE); HOT TEMPERATURE; HYPERALGESIA; IRRITANTS; MALE; MICE; PAIN MEASUREMENT; RATS; RATS, WISTAR; RECEPTORS, OPIOID, DELTA; RESPIRATORY INSUFFICIENCY; SEIZURES; SELF ADMINISTRATION; STOMACH ULCER; SUBSTANCE WITHDRAWAL SYNDROME; SUBSTANCE-RELATED DISORDERS; XANTHENES; ZYMOSAN;

EID: 63849100896     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.108.146969     Document Type: Article

References (33)

1. Baldrick P, Bamford DG, and Tattersall ML (1998) An assessment of two gastric transport models currently used in safety pharmacology testing. Hum Exp Toxicol 17:1-7.
2. Bilsky EJ, Calderon SN, Wang T, Bernstein RN, Davis P, Hruby VJ, McNutt RW, Rothman RB, Rice KC, and Porreca F (1995) SNC 80, a selective, nonpeptidic and systemically active opioid delta agonist. J Pharmacol Exp Ther 273:359-366.
3. Brandt MR, Furness MS, Mello NK, Rice KC, and Negus SS (2001) Antinociceptive effects of δ-opioid agonists in rhesus monkeys: effects on chemically induced thermal hypersensitivity. J Pharmacol Exp Ther 296:939-946.
4. Cahill CM, Morinville A, Hoffert C, O'Donnell D, and Beaudet A (2003) Up- regulation and trafficking of δ opioid receptor in a model of chronic inflammation: implications for pain control. Pain 101:199-208.
5. Carson JR, Coats SJ, Codd EE, Dax SL, Lee J, Martinez RP, Neilson LA, Pitis PM, and Zhang SP (2004) N,N-Dialkyl-4-[(8-azabicyclo[3.2.1]-oct-3-ylidene) phenylm-ethyl]benzamides, potent, selective δ opioid agonists. Bioorg Med Chem Lett 14:2109-2112.
6. Coats SJ, Schulz MJ, Carson JR, Codd EE, Hlasta DJ, Pitis PM, Stone DJ Jr, Zhang SP, Colburn RW, and Dax SL (2004) Parallel methods for the preparation and SAR exploration of N-ethyl-4-[(8-alkyl-8-aza-bicyclo[3.2.1]oct-3- ylidene)-aryl-methyl]- benzamides, powerful mu and delta opioid agonists. Bioorg Med Chem Lett 14:5493-5498.
7. Codd EE, Carson JR, Colburn RW, Dax SL, Desai-Krieger D, Martinez RP, McKown LA, Neilson LA, Pitis PM, Stahle PL, et al. (2006) The novel, orally active, delta opioid RWJ-394674 is biotransformed to the potent mu opioid RWJ-413216. J Pharmacol Exp Ther 318:1273-1279.
8. Collier HO, Dinneen LC, Johnson CA, and Schneider C (1968) The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother 32:295-310.
9. Dondio G, Ronzoni S, Farina C, Graziani D, Parini C, Petrillo P, and Giardina GAM (2001) Selective δ opioid receptor agonists for inflammatory and neuropathic pain. Farmaco 56:117-119.
10. Feschenko MS, Dave KD, and Windh RT (2006) Agonist-specific resensitization of the delta opioid receptor. FASEB J 20:A251.
11. Galandrin S, Oligny-Longpré G, and Bouvier M (2007) The evasive nature of drug efficacy: implications for drug discovery. Trends Pharmacol Sci 28:423-430.
12. Gebhart GF, Su X, Joshi S, Ozaki N, and Sengupta JN (2000) Peripheral opioid modulation of visceral pain. Ann N Y Acad Sci 909:41-50.
13. Hardman JG and Limbird LE (2001) Goodman & Gilman's The Pharmacological Basis of Therapeutics, McGraw-Hill, New York.
14. Hargreaves K, Dubner R, Brown F, Flores C, and Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77-88.
15. 5]-enkephalin (DPDPE) analgesia in mice. NIDA Res Monogr 75:442-445.
16. Hurley RW and Hammond DL (2000) The analgesic effects of supraspinal mu and delta opioid receptor agonists are potentiated during persistent inflammation. J Neurosci 20:1249-1259.
17. Jutkiewicz EM, Rice KC, Traynor JR, and Woods JH (2005) Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats. Psychopharmacology (Berl) 182:588-596.
18. Kamei J, Kawai K, Mizusuna A, Saitoh A, Morita K, Narita M, Tseng LF, and Nagase H (1997) Supraspinal delta 1-opioid receptor-mediated antinociceptive properties of (-)-TAN-67 in diabetic mice. Eur J Pharmacol 322:27-30.
19. Kamei J, Saitoh A, Ohsawa M, Suzuki T, Misawa M, Nagase H, and Kasuya Y(1995) Antinociceptive effects of the selective non-peptidic delta-opioid receptor agonist TAN-67 in diabetic mice. Eur J Pharmacol 276:131-135.
20. Kim SH and Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50:355-363.
21. Le Bourdonnec B, Windh RT, Ajello CW, Leister LK, Gu M, Chu GH, Tuthill PA, Barker WM, Koblish M, Wiant DD, et al. (2008) Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5- hydroxyspiro[chromene-2,4′-piperidine]-4-yl)benzamide (ADL5859). J Med Chem 51:5893-5896.
22. Lee PH, McNutt RW, and Chang KJ (1993) A nonpeptidic delta opioid receptor agonist, BW373U86, attenuates the development and expression of morphine abstinence precipitated by naloxone in rat. J Pharmacol Exp Ther 267:883-887.
23. McKnight AT, Corbett AD, Marcoli M, and Kosterlitz HW(1985) The opioid receptors in the hamster vas deferens are of the delta type. Neuropharmacology 24:1011-1017.
24. Nagakura Y, Naitoh Y, Kamato T, Yamano M, and Miyata K (1996) Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal propulsion in mice. Eur J Pharmacol 311:67-72.
25. O'Neill SJ, Collins MA, Pettit HO, McNutt RW, and Chang KJ (1997) Antagonistic modulation between the delta opioid agonist BW373U86 and the mu opioid agonist fentanyl in mice. J Pharmacol Exp Ther 282:271-277.
26. Petrillo P, Angelici O, Bingham S, Ficalora G, Garnier M, Zaratin PF, Petrone G, Pozzi O, Sbacchi M, Stean TO, et al. (2003) Evidence for a selective role of the δ-opioid agonist [8R-(46S*,8aa,8ab,12bb)]7,10-dimethyl- 1-methoxy-11-(2- methylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro- (9h)-4,8-methanobenzo- furo[3,2-e]pyrrolo[2,3-g]isoquinoline hydrochloride (SB-235863) in blocking hyper- algesia associated with inflammatory and neuropathic pain responses. J Pharmacol Exp Ther 307:1079-1089.
27. RandallLOand Selitto JJ(1957) A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther 111:409-419.
28. Rodriguez RE, Leighton G, Hill RG, and Hughes J (1986) In vivo evidence for spinal delta-opiate receptor-operated antinociception. Neuropeptides 8:221-241.
29. Smits SE (1975) Quantitation of physical dependence in mice by naloxone- precipitated jumping after a single dose of morphine. Res Commun Chem Pathol Pharmacol 10:651-661.
30. Stevenson GW, Folk JE, Rice KC, and Negus SS (2005) Interactions between delta and mu opioid agonists in assays of schedule-controlled responding, thermal nociception, drug self-administration, and drug versus food choice in rhesus monkeys: studies with SNC80 [(+ )-4-[(aR)-a-((2S,5R)-4-allyl-2,5- dimethyl-1- piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] and heroin. J Pharmacol Exp Ther 314:221-231.
31. Su YF, McNutt RW, and Chang KJ (1998) Delta-opioid ligands reverse alfentanil-induced respiratory depression but not antinociception. J Pharmacol Exp Ther 287:815-823.
32. Sundaresan N, DiGiacinto GV, and Hughes JE (1989) Neurosurgery in the treatment of cancer pain. Cancer 63:2365-2377.
33. Tseng LF, Narita M, Mizoguchi H, Kawai K, Mizusuna A, Kamei J, Suzuki T, and Nagase H (1997) Delta-1 opioid receptor-mediated antinociceptive properties of a nonpeptidic delta opioid receptor agonist, (- )-TAN-67, in the mouse spinal cord. JPharmacol Exp Ther 280:600-605.