Apadoline

Apadoline
Clinical data
Other namesRP-60180; RP60180; RP-60,180; RP-60180A
Drug classκ-Opioid receptor agonist
ATC code
  • None
Identifiers
  • N-propyl-10-[(2R)-1-pyrrolidin-1-ylpropan-2-yl]phenothiazine-2-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H29N3OS
Molar mass395.57 g·mol−1
3D model (JSmol)
  • CCCNC(=O)C1=CC2=C(C=C1)SC3=CC=CC=C3N2[C@H](C)CN4CCCC4
  • InChI=1S/C23H29N3OS/c1-3-12-24-23(27)18-10-11-22-20(15-18)26(17(2)16-25-13-6-7-14-25)19-8-4-5-9-21(19)28-22/h4-5,8-11,15,17H,3,6-7,12-14,16H2,1-2H3,(H,24,27)/t17-/m1/s1
  • Key:KXMAIWXPZGQNCR-QGZVFWFLSA-N

Apadoline (INNTooltip International Nonproprietary Name; developmental code name RP-60180) is a κ-opioid receptor agonist and experimental analgesic which was under development for the treatment of cancer pain but was never marketed. It produces effects and adverse effects in humans including analgesia, drowsiness, and headache, among others. Its affinities (Ki) for the opioid receptors are 0.55 nM for the κ-opioid receptor, 11.4 nM for the δ-opioid receptor, and 57 nM for the μ-opioid receptor. Apadoline was first described in the scientific literature by 1990. It was under development by Rhône-Poulenc in the 1990s and reached phase 2 clinical trials prior to the discontinuation of its development. An analogue with greater potency, RP-61127, has also been described.

See also

References

  1. 1 2 "Apadoline". AdisInsight. 9 October 2001. Retrieved 15 May 2026.
  2. 1 2 "Delving into the Latest Updates on Apadoline with Synapse". Synapse. 21 March 2026. Retrieved 15 May 2026.
  3. 1 2 3 Barber A, Gottschlich R (October 1997). "Novel developments with selective, non-peptidic kappa-opioid receptor agonists". Expert Opinion on Investigational Drugs. 6 (10): 1351–1368. doi:10.1517/13543784.6.10.1351. PMID 15989506.
  4. 1 2 Szmuszkovicz J (1999). "U-50,488 and the к receptor Part II: 1991–1998". Progress in Drug Research. Basel: Birkhäuser Basel. pp. 1–51. doi:10.1007/978-3-0348-8735-9_1. ISBN 978-3-0348-9749-5.
  5. 1 2 Lötsch J, Ditterich W, Hummel T, Kobal G (June 1997). "Antinociceptive effects of the kappa-opioid receptor agonist RP 60180 compared with pentazocine in an experimental human pain model". Clinical Neuropharmacology. 20 (3): 224–233. doi:10.1097/00002826-199706000-00006. PMID 9197945.
  6. ↑ Fardin V, Plau B, Carruette A, Guyon C, Bardon T, Taurand G, et al. (1990). "RP 60180: A novel phenothiazine with high affinity for kappa binding sites and with antinociceptive effects in rodents". Pain. 41: S192. doi:10.1016/0304-3959(90)92520-Z.
  7. ↑ Fardin V, Jolly A, Flamand O, Carruette A, Laduron PM, Garret C (1990). "RP 60180, a new phenothiazine with high affinity for opiate kappa binding sites in animal and human brain". European Journal of Pharmacology. 183 (6): 2332. doi:10.1016/0014-2999(90)93890-3.
  8. ↑ Raghubir R, Patnaik GK, Sharma SD, Mathur KB, Dhawan BN (1990). "A parentrally active highly potent analgesic peptide with reduced abuse potential". Pain. 41: S192. doi:10.1016/0304-3959(90)92521-Q.
  9. ↑ Reibaud, M., Stutzmann, J. M., Böhme, G. A., Lafforgue, J., Garret, C., & Laduron, P. M. (1990). Electrocorticograpnic profile and discriminative stimulus properties of RP 60180, a new kappa agonist. European Journal of Pharmacology, 183(6), 2331. https://scholar.google.com/scholar?cluster=6360720396979939973
  10. ↑ Boireau A, Dubedat P, Laduron P, Blanchard JC, Doble A, Garret C (1990). "Effects of RP 60180, a kappa-receptor agonist, on dopamine metabolism and utilization in rat and guinea-pig brain". European Journal of Pharmacology. 183 (6): 2330. doi:10.1016/0014-2999(90)93888-W.