2. Academic Validation
  3. Receptor affinities of dopamine D1 receptor-selective novel phenylbenzazepines

Receptor affinities of dopamine D1 receptor-selective novel phenylbenzazepines

  • Eur J Pharmacol. 2003 Aug 8;474(2-3):137-40. doi: 10.1016/s0014-2999(03)02008-9.
John L Neumeyer 1,  Nora S Kula,  Jack Bergman,  Ross J Baldessarini
Affiliations

Affiliation

  • 1 Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA, USA. [email protected]
PMID: 12921854 DOI: 10.1016/s0014-2999(03)02008-9
Abstract

We prepared a series of 18 novel substituted phenylbenzazepine congeners of the dopamine D1/D5 receptor partial-agonist SKF-83959 (R,S-3-methyl-6-chloro-7,8-dihydroxy-1-[3'-methylphenyl]-2,3,4,5-tetrahydro-1H-benzazepine) and characterized their potency and selectivity in assays of dopamine, 5-HT and adrenoceptors in rat brain tissue or membranes of genetically transfected cells. The R-enantiomer of SKF-83959 (MCL-202) and three other novel racemic 1-phenyl-7,8-dihydroxybenzazepines (MCL-204, -203, and -207) showed very high dopamine D5 receptor affinity; MCL-209 displayed the greatest dopamine D5 receptor affinity. These five potent novel ligands also had >100-fold selectivity for dopamine D1 over dopamine D2, D3, serotonin 5-HT-2A receptors and alpha2-adrenoceptors. They require further functional testing to characterize their intrinsic activity, and for potential stimulant-antagonist actions, as observed with SKF-83959 and MCL-202.

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