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KMID : 0811719980020040461
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Korean Journal of Physiology & Pharmacology
1998 Volume.2 No. 4 p.461 ~ p.469
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Pharmacological Characterization of Synthetic Tetrahydroisoquinoline Alkaloids, YS 51 and YS 55, on the Cardiovascular System
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Ki-Churl Chang
Young-Jin Kang/Young-Soo Lee/Won-Seog Chong/Hye-Sook Yun-Choi 3Duck-Hyong Lee/Jae-Chun Ryu
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Abstract
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Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethy-lamines, 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 ?β?receptor activities. However, it is not clear whether -OH at 6,7 substitution of THIs also shows ?α?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?β?naphthylmethyl?6,7?dihydroxy?1,2,3,4?tetrahydroisoquinoline HBr (YS 51) and 1?β?naphthylmethyl?6,7?dimethoxy?1,2,3,4?tetrahydroisoquinoline HCl (YS 55), and their pharmacological actions on ?α1?adrenoceptor were compared. YS 51 and YS 55, concentration-dependently relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 μM) 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 μM 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 μM 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 μM, 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.
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