Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines, and many of them, especially with 6,7-disubstitution, demonstrate relatively high affinity for catecholamines. Two -OH groups at 6 and 7 positions are supposed to be essential to exert ㄂-receptor activities. However, it is not clear whether -OH at 6,7 substitution of THIs also shows ㄁-adrenoceptor activities. In the present study, we investigated whether -OH or -OCH3 substitutions of 6,7 position of THIs differently affect the ㄁1-adrenoceptor affinity. We synthesized two 1-naphthylmethyl THI alkaloids, 1-㄂-naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline HBr (YS 51) and 1-㄂-naphthylmethyl-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline HCl (YS 55), and their pharmacological actions on ㄁1-adrenoceptor were compared. YS 51 and YS 55, concentration-dependently relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ㄍM) in which pEC50 were 5.89⁢0.21 and 5.93⁢0.19, respectively. Propranolol (30 nM) did not affect the relaxation-response curves to YS 51 and YS 55. Concentration-response curves to PE were shifted to right by the pretreatment with YS 51 or YS 55. The pA2 values of YS 51 and YS 55 showed 6.05⁢0.24 and 5.88⁢0.16, respectively. Both probes relaxed KCl (65.4 mM)-contracted aorta and inhibited CaCl2-induced contraction of PE-stimulated endothelium- denuded rat thoracic aorta in Ca2⁢-free solutions. In isolated guinea pig papillary muscle, 1 and 10 ㄍM YS 51 increased contractile force about 4- and 8- fold over the control, respectively, along with the concentration-dependent increment of cytosolic Ca2⁢ ions. While, 10 ㄍM YS 55 reduced the contractile force about 50 % over the control and lowered the cytosolic Ca2⁢ level, in rat brain homogenates, YS 51 and YS 55 displaced [3H]prazosin binding competitively with Ki 0.15 and 0.12 ㄍM, respectively. However, both probes were ineffective on [3H]nitrendipine binding. Therefore, it is concluded that two synthetic naphthylmethyl-THI alkaloids have considerable affinity to ㄁1-adrenenoceptors in rat aorta and brain.