[Antagonistic characterization of 1-(2,6-dimethylphenoxyl)-2-(3,4-dimethylphenyl ethylamino) propane hydrochloride on alpha 1-adrenoceptor].
OBJECTIVE
To study the antagonistic effect of 1-(2,6-dimethylphenox)-2-(3,4-dimethylphenyl ethylamino) propane hydrochloride (DDPH) on alpha 1-adrenoceptor (AR).


METHODS
Radioligand binding assay was used. Specific 125I-BE2254 (2-beta(4-hydroxyphenyl)-ethyl aminomethyl-tetralone) binding was measured by incubating membrane of rat cerebral cortex, spleen and the three cloned alpha 1-AR subtypes (alpha 1A, alpha 1B, alpha 1D) stably expressed in human embryonic kidney 293 cell preparation with a single concentration of 125I-BE2254 in the presence of 14 concentrations of DDPH. Equilibrium binding constant (KI) and Hill coefficients (nH) were determined from Hill plots. The -log value of the KI was expressed as pKI. Contractile responses of isolated rat aorta, renal artery ring and spleen were determined. The pA2 values for DDPH in competitively inhibiting NE-stimulated contraction of tissues were measured with the method of Ainlakshana and Schild.


RESULTS
DDPH competitively inhibited binding of 125I-BE2254 to alpha 1-AR in a concentration-dependent manner. The pKI values for DDPH in rat cerebral cortex and spleen were 7.17 +/- 0.06 and 7.41 +/- 0.11, respectively, and the Hill efficiency values were not significantly different from unit. The pKI values for cloned alpha 1A, alpha 1B and alpha 1D-AR were 7.21 +/- 0.12, 6.88 +/- 0.04 and 7.26 +/- 0.06, respectively, and the Hill efficiency values were not significantly different from unit. Contractile studies showed that DDPH competitively antagonized the NE concentration-response curve with a pA2 values of 7.40 +/- 0.23 in aorta, 7.41 +/- 0.04 in renal artery and 7.63 +/- 0.07 in spleen and the slopes of schild plot were not significantly different from unit. The pKI values for DDPH in tissues and the cloned alpha 1A or alpha 1D-AR were shown to fit well in with the pA2 values in antagonizing NE-induced constriction in rat isolated aorta, renal artery and spleen.


CONCLUSIONS
These results suggest that DDPH appear to be a non-subtype selective competitive antagonist for alpha 1-AR.
Lu
Z Z
ZZ
Institute of Vascular Medicine, Third Hospital, Beijing Medical University, Beijing 100083, China.
Zhang
Y Y
YY
Xia
L
L
Han
Q D
QD
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D010627:Phenethylamines; C057485:1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane