SKF-81,297

SKF-81,297
Clinical data
Other names	SKF81297; SKF-81297; SK&F-81297; SK&F-81,297; SK&F81297
Routes of; administration	Oral
Drug class	Dopamine receptor agonist; Dopamine D1-like receptor agonist; Stimulant; Antiparkinsonian agent
ATC code	None;
Identifiers
	IUPAC name 9-chloro-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol;
CAS Number	71636-61-8 ;
PubChem CID	1218;
ChemSpider	1181;
UNII	9GBP09E08K;
ChEBI	CHEBI:91517;
ChEMBL	ChEMBL353335;
CompTox Dashboard (EPA)	DTXSID3058743 ;
Chemical and physical data
Formula	C16H16ClNO2
Molar mass	289.76 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CNCC(C2=CC(=C(C(=C21)Cl)O)O)C3=CC=CC=C3;
	InChI 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. It is a cyclized phenethylamine and catecholamine and is a modified derivative of the monoamine neurotransmitter dopamine. The drug is taken orally.

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.

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.

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.

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.