SKF-81,297

SKF-81,297
Clinical data
Other namesSKF81297; SKF-81297; SK&F-81297; SK&F-81,297; SK&F81297
Routes of
administration		Oral[1]
Drug classDopamine receptor agonist; Dopamine D1-like receptor agonist; Stimulant; Antiparkinsonian agent
ATC code
  • None
Identifiers
  • 9-chloro-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC16H16ClNO2
Molar mass289.76 g·mol−1
3D model (JSmol)
  • C1CNCC(C2=CC(=C(C(=C21)Cl)O)O)C3=CC=CC=C3
  • InChI=1S/C16H16ClNO2/c17-15-11-6-7-18-9-13(10-4-2-1-3-5-10)12(11)8-14(19)16(15)20/h1-5,8,13,18-20H,6-7,9H2
  • Key:GHWJEDJMOVUXEC-UHFFFAOYSA-N

SKF-81,297 is a dopamine D1-like receptor agonist and stimulant-like drug of the 3-benzazepine family which was under development for the treatment of Parkinson's disease but was never marketed.[1][2][3] It is a cyclized phenethylamine and catecholamine and is a modified derivative of the monoamine neurotransmitter dopamine.[4] The drug is taken orally.[1]

The drug acts as a selective dopamine D1 and D5 receptor full agonist.[3] In addition, it acts as a partial agonist at dopamine D1–D2 receptor heteromers.[5] It produces a characteristic stimulant-like pattern of effects including anorexia, hyperactivity, and self-administration in animals.[3] This profile is shared with several related drugs such as 6-Br-APB and SKF-82,958,[6] but not with certain other dopamine D1 receptor full agonists such as A-77,636, reflecting functional selectivity of dopamine D1 receptor activation.[7][8][9] The drug also produces pro-motivational effects in animals.[10]

Although it produces stimulant-like effects in animals, SKF-81,297 did not substitute for dextroamphetamine in rodent drug discrimination tests in multiple studies.[11][12] This is in notable contrast to dopamine D2 receptor agonists like quinpirole and RU-24213, which fully substitute for dextroamphetamine in such tests.[13] However, in another study, higher doses of SKF-81,297 were able to partially substitute for dextroamphetamine.[13]

SKF-81,297 readily crosses the blood–brain barrier in rodents and shows substantially greater penetration than the related dopamine D1-like receptor agonist SKF-38,393.[12] Its predicted log P is 2.7.[14]

SKF-81,297 was first described in the scientific literature by 1988.[15] It was developed by GlaxoSmithKline.[1][2] The drug reached the preclinical research stage of development for Parkinson's disease prior to the discontinuation of its development.[1][2] One of the patented uses for SKF-81,297 is as an augmentation agent when combined with an appropriate choice of an antidepressant.[16]

See also

References

  1. ^ a b c d e "SKF 81297". AdisInsight. 22 January 2008. Retrieved 16 February 2026.
  2. ^ a b c "Delving into the Latest Updates on SKF-81297 with Synapse". Synapse. 15 November 2025. Retrieved 16 February 2026.
  3. ^ a b c Weed MR, Vanover KE, Woolverton WL (1993). "Reinforcing effect of the D1 dopamine agonist SKF 81297 in rhesus monkeys". Psychopharmacology. 113 (1): 51–2. doi:10.1007/BF02244333. PMID 7862828. S2CID 7292320.
  4. ^ Felsing DE, Jain MK, Allen JA (2019). "Advances in Dopamine D1 Receptor Ligands for Neurotherapeutics". Curr Top Med Chem. 19 (16): 1365–1380. doi:10.2174/1568026619666190712210903. PMID 31553283.
  5. ^ Rashid AJ, So CH, Kong MM, et al. (2007). "D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum". Proc. Natl. Acad. Sci. U.S.A. 104 (2): 654–9. Bibcode:2007PNAS..104..654R. doi:10.1073/pnas.0604049104. PMC 1766439. PMID 17194762.
  6. ^ Weed MR, Paul IA, Dwoskin LP, Moore SE, Woolverton WL (October 1997). "The relationship between reinforcing effects and in vitro effects of D1 agonists in monkeys". The Journal of Pharmacology and Experimental Therapeutics. 283 (1): 29–38. PMID 9336305.
  7. ^ Chausmer AL, Katz JL (January 2002). "Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents". Psychopharmacology. 159 (2): 145–53. doi:10.1007/s002130100896. PMID 11862342. S2CID 6788631.
  8. ^ Graham DL, Hoppenot R, Hendryx A, Self DW (April 2007). "Differential ability of D1 and D2 dopamine receptor agonists to induce and modulate expression and reinstatement of cocaine place preference in rats". Psychopharmacology. 191 (3): 719–30. doi:10.1007/s00213-006-0473-5. PMID 16835769. S2CID 21192319.
  9. ^ Delfino M, Kalisch R, Czisch M, Larramendy C, Ricatti J, Taravini IR, Trenkwalder C, Murer MG, Auer DP, Gershanik OS (September 2007). "Mapping the effects of three dopamine agonists with different dyskinetogenic potential and receptor selectivity using pharmacological functional magnetic resonance imaging". Neuropsychopharmacology. 32 (9): 1911–21. doi:10.1038/sj.npp.1301329. PMID 17287822.
  10. ^ Yohn SE, Santerre JL, Nunes EJ, Kozak R, Podurgiel SJ, Correa M, Salamone JD (August 2015). "The role of dopamine D1 receptor transmission in effort-related choice behavior: Effects of D1 agonists". Pharmacol Biochem Behav. 135: 217–226. doi:10.1016/j.pbb.2015.05.003. PMID 26022661.
  11. ^ Reavill C, Bond B, Overend P, Hunter AJ (April 1993). "Pharmacological characterization of the discriminative stimulus properties of the dopamine D1 agonist, SKF 81297". Behav Pharmacol. 4 (2): 135–146. doi:10.1097/00008877-199304000-00006. PMID 11224180.
  12. ^ a b Nielsen EB, Randrup K, Andersen PH (January 1989). "Amphetamine discrimination: effects of dopamine receptor agonists". Eur J Pharmacol. 160 (2): 253–262. doi:10.1016/0014-2999(89)90498-6. PMID 2569406.
  13. ^ a b Furmidge LJ, Exner M, Clark D (September 1991). "Role of dopamine D1 and D2 receptors in mediating the d-amphetamine discriminative cue". Eur J Pharmacol. 202 (2): 191–199. doi:10.1016/0014-2999(91)90294-z. PMID 1687032.
  14. ^ "SK&F 81297". PubChem. Retrieved 16 February 2026.
  15. ^ Arnt, J., Bøgesø, K. P., & Hyttel, J. (1988, June). Dopamine D-1 and D-2 receptor differentiation revealed by behavioural studies in rats. In Pharmacology and Functional Regulation of Dopaminergic Neurons: Proceedings of a Satellite Symposium of the IUPHAR 10th International Congress of Pharmacology, 31 August–2 September 1987 (pp. 110-116). London: Palgrave Macmillan UK. https://doi.org/10.1007/978-1-349-10047-7_17
  16. ^ Akinori Nishi, et al. WO2012127871 (Kurume University, Nippon Medical School Foundation, Fujita Educational Inst, Rockefeller University).
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