title: The pKa of butaclamol and the mode of butaclamol binding to central dopamine receptors.
abstract: The pKa values for butaclamol (1), 1,2,3,5,6,10b beta-hexahydro-6 alpha-phenylpyrrolo[2,1-alpha]isoquinoline (2, McN-4612-Y), and 2-tert-butyl-1,3,4,6,7,11b beta-hexahydro-7 beta-phenyl-2H-benzo[alpha]quinolizin-2 alpha-ol (3, McN-4171) were determined to be 7.2, 9.1, and 7.0, respectively. The values for 1 and 3 are anomalous; however, the value for 1 (7.2) is not as low as the one reported in the literature (pKa = 5.9). We also determined pKa values for apomorphine, chlorpromazine, and lidocaine, for reference purposes (7.6, 9.2, and 7.9, respectively). The results indicate that 1 would not be predominantly unprotonated under the physiological conditions of receptor binding, rather it would be about 50% protonated. This fact may contravene a suggested binding model used to map the central dopamine receptor (viz., ref 3).
authors.forename: F A
authors.initials: FA
authors.lastname: Chrzanowski
authors.forename: B A
authors.initials: BA
authors.lastname: McGrogan
authors.forename: B E
authors.initials: BE
authors.lastname: Maryanoff
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002069:Butaclamol / Q000378:metabolism*; D003986:Dibenzocycloheptenes / Q000378:metabolism*; D006801:Humans; D011954:Receptors, Dopamine / Q000378:metabolism*
chemical_list: D003986:Dibenzocycloheptenes; D011954:Receptors, Dopamine; D002069:Butaclamol