SKF-81,297 explained

SKF-81,297 is a synthetic drug of the benzazepine chemical class that acts as a selective dopamine D₁/D₅ receptor full agonist, and produces a characteristic stimulant-like pattern of anorexia, hyperactivity and self-administration in animals.^[1] This profile is shared with several related drugs such as 6-Br-APB and SKF-82,958,^[2] but not with certain other D₁ full agonists such as A-77,636, reflecting functional selectivity of D₁ activation.^{[3] [4] [5]} Newer findings reveal that SKF-81,297 additionally acts as a partial agonist at D₁-D₂ receptor heteromers.^[6]

One of the patented uses for SKF-81,297 is as an augmentation agent when combined with an appropriate choice of an antidepressant.^[7]

Notes and References

1. Weed MR, Vanover KE, Woolverton WL . Reinforcing effect of the D1 dopamine agonist SKF 81297 in rhesus monkeys . Psychopharmacology . 113 . 1 . 51–2 . 1993 . 7862828 . 10.1007/BF02244333. 7292320 .
2. 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 . 283 . 1 . 29–38 . October 1997 . 9336305 .
3. 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 . 159 . 2 . 145–53 . January 2002 . 11862342 . 10.1007/s002130100896 . 6788631 .
4. 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 . 191 . 3 . 719–30 . April 2007 . 16835769 . 10.1007/s00213-006-0473-5 . 21192319 .
5. 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 . 32 . 9 . 1911–21 . September 2007 . 17287822 . 10.1038/sj.npp.1301329 . free .
6. 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. . 104 . 2 . 654–9 . 2007 . 17194762 . 1766439 . 10.1073/pnas.0604049104 . 2007PNAS..104..654R . free .
7. Akinori Nishi, et al. WO2012127871 (Kurume University, Nippon Medical School Foundation, Fujita Educational Inst, Rockefeller University).