ANTAGONISTIC EFFECT OF TETKAHYDKOPROBERBEKINE HOMOLOGUES ON α₁-ADRENOCEPTOR

The antagonistic effect of tetrahydroproberberine(THP)homologues on α₁-adrenoceptor was studied by combination of radioligand binding assays and measurements ofvasoconstriction responses.The results showed that l-tetrahydropalmatine(l-THP),l- stepholidine(l-SPD),THPB-18 and tetrahydroberberine(THB)competitively inhibited the 125 I-BE2254 specificbinding in rat cerebral cortex with pK_I values of 5.54±0.36,5.56±0.47,5.75±0.56 and 6.01 ±0.60,respectively,and the Hill efficiency was not significantly different from unity.They inhibitedphenylephrine-induced constrictions with pA₂ values of 5.48 ± 0.58,5.66 ± 0.54,5.64 ± 0.34 and5.45 ± 0.76,respectively,and the slopes of Schild plot were not significantly different from unity。The results indicate that the 4 THP homologues are nonsubtype selective competitive antagonists forα₁