1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene (H2-PAT): Effect of stereochemistry on binding and function at brain histamine receptors
Document Type
Article
Publication Title
Medicinal Chemistry Research
Abstract
We report the synthesis, separation, receptor binding, and functional effects on mammalian brain dopamine synthesis of the isomers of 1-phenyl-3- dimethylamino-1,2,3,4-tetrahydronaphthalene (1-phenyl-3-aminotetralin, H2- PAT). The trans-(1R,3S)-(-)-H2-PAT isomer has highest affinity (K0.5 ~ 0.3 and 1.4 nM, respectively) and the cis-(1R,3R)-(+) isomer has lowest affinity (K0.5 ~ 70 and 340 nM, respectively) at histamine H1-type receptors labeled by [3H]-trans(-)-H2-PAT and [3H]-mepyramine in guinea pig brain. In general, our results suggest that stereochemistry at C1 and especially C3 is critically important for affinity of PAT and other diarylaminopropane-containing molecules at histamine H1-type receptors. At 1.0 μM, the two H2-PAT diastereomeric pairs and the racemates stimulate dopamine synthesis by activation of tyrosine hydroxylase to a similar extent (ca. 120% of control). These results are discussed in light of recent findings that [3H]-trans(-)-H2-PAT may radiolabel a presynaptic subpopulation of histamine H1-type receptors in mammalian forebrain.
First Page
322
Last Page
332
Publication Date
12-1-1998
Recommended Citation
Bucholtz, Ehren C.; Wyrick, Steven D.; Owens, Constance E.; Mcphail, Andrew T.; and Booth, Raymond G., "1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene (H2-PAT): Effect of stereochemistry on binding and function at brain histamine receptors" (1998). Basic Sciences Faculty Publications. 24.
https://collections.uhsp.edu/basic-sciences_pubs/24