SKF-81,297

Overview

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. It is a cyclized phenethylamine and catecholamine and is a modified derivative of the monoamine neurotransmitter dopamine. The drug is taken orally.[1–4] WP

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

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

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. Its predicted log P is 2.7.[12][14] WP

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

Drug class

Dopamine receptor agonist Dopamine D1-like receptor agonist Stimulant Antiparkinsonian agent WP

From the Wikipedia article's infobox.

Chemistry

Formula

C16H16ClNO2 PC

CAS number

71636-61-8 PC

Molar mass (g/mol)

289.75 PC

IUPAC name (computed by PubChem)

9-chloro-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol PC

SMILES

C1CNCC(C2=CC(=C(C(=C21)Cl)O)O)C3=CC=CC=C3 PC

InChIKey

GHWJEDJMOVUXEC-UHFFFAOYSA-N PC

PubChem CID

1218

IUPAC name

9-chloro-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol WP

Mixing

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency SKF 81297. 22 January 2008
2. Other Delving into the Latest Updates on SKF-81297 with Synapse. 15 November 2025
3. Journal / agency Weed MR, Vanover KE, Woolverton WL. Reinforcing effect of the D1 dopamine agonist SKF 81297 in rhesus monkeys. Psychopharmacology. 1993. doi:10.1007/BF02244333 · PMID 7862828
4. Journal / agency Felsing DE, Jain MK, Allen JA. Advances in Dopamine D1 Receptor Ligands for Neurotherapeutics. Curr Top Med Chem. 2019. doi:10.2174/1568026619666190712210903 · PMID 31553283
5. Journal / agency Rashid AJ, So CH, Kong MM, etal. 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. 2007. doi:10.1073/pnas.0604049104 · PMID 17194762 · PMC1766439
6. Journal / agency Weed MR, Paul IA, Dwoskin LP, Moore SE, Woolverton WL. The relationship between reinforcing effects and in vitro effects of D1 agonists in monkeys. The Journal of Pharmacology and Experimental Therapeutics. October 1997. PMID 9336305
7. Journal / agency Chausmer AL, Katz JL. 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. January 2002. doi:10.1007/s002130100896 · PMID 11862342
8. Journal / agency Graham DL, Hoppenot R, Hendryx A, Self DW. Differential ability of D1 and D2 dopamine receptor agonists to induce and modulate expression and reinstatement of cocaine place preference in rats. Psychopharmacology. April 2007. doi:10.1007/s00213-006-0473-5 · PMID 16835769
9. Journal / agency Delfino M, Kalisch R, Czisch M, Larramendy C, Ricatti J, Taravini IR, Trenkwalder C, Murer MG, Auer DP, Gershanik OS. Mapping the effects of three dopamine agonists with different dyskinetogenic potential and receptor selectivity using pharmacological functional magnetic resonance imaging. Neuropsychopharmacology. September 2007. doi:10.1038/sj.npp.1301329 · PMID 17287822
10. Journal / agency Yohn SE, Santerre JL, Nunes EJ, Kozak R, Podurgiel SJ, Correa M, Salamone JD. The role of dopamine D1 receptor transmission in effort-related choice behavior: Effects of D1 agonists. Pharmacol Biochem Behav. August 2015. doi:10.1016/j.pbb.2015.05.003 · PMID 26022661
11. Journal / agency Reavill C, Bond B, Overend P, Hunter AJ. Pharmacological characterization of the discriminative stimulus properties of the dopamine D1 agonist, SKF 81297. Behav Pharmacol. April 1993. doi:10.1097/00008877-199304000-00006 · PMID 11224180
12. Journal / agency Nielsen EB, Randrup K, Andersen PH. Amphetamine discrimination: effects of dopamine receptor agonists. Eur J Pharmacol. January 1989. doi:10.1016/0014-2999(89)90498-6 · PMID 2569406
13. Journal / agency Furmidge LJ, Exner M, Clark D. Role of dopamine D1 and D2 receptors in mediating the d-amphetamine discriminative cue. Eur J Pharmacol. September 1991. doi:10.1016/0014-2999(91)90294-z · PMID 1687032
14. Journal / agency SK&F 81297
15. Journal / agency 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
16. Other Akinori Nishi, et al. WO2012127871 (Kurume University, Nippon Medical School Foundation, Fujita Educational Inst, Rockefeller University)

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