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Journal of Korean Neurosurgical Society 1999;28(1): 5-12.
Effect of Tetrahydroisoquinoline Alkaloids on the alpha-adrenoceptors in Rat Aorta and Brain Homogenates.
Hyun Seok Lee, Sun Ha Paek, Soo Hyun Hwang, In Sung Park, Eun Sang Kim, Myung Jin Jung, Jong Woo Han, Ki Churl Chang
1Department of Neurosurgery, College of Medicine, Gyeongsang National University, Chinju, Korea.
2Department of Pharmacology, College of Medicine, Gyeongsang National University, Chinju, Korea.
3Department of Cardiovascular Research Institute, College of Medicine, Gyeongsang National University, Chinju, Korea.
ABSTRACT
Tetrahydroisoquinoline(THI) alkaloids can be considered as cyclized derivatives of simple pthylamines and many of them, especially with 6,7-disubstitution, demonstrate relatively high affinity for catecholamines. In the present study, pharmacological action of limited series of THI has been examined using rat isolated atria and aorta. In addition, (H) prazosin displacement binding study with THI compounds using rat brain homogenates was performed to find out if these probes to have a-adrenoceptor affinity. In isolated rat atria, all THls and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right resulting in 8.07+0.84 and 7. 93+0.11 of pA values, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac beta1-adrenoceptors. YS 49, YS 51 and higenamine showed alpha1- adrenoceptor affinity in rat brain in which the dissociation constant(K,) was 2.75, 2.81 and 1.02pM, respectively. It is concluded, therefore, that THI alkaloids have considerable affiniyt to alpha1-adrenoceptors in rat aorta and atria. while these probes show relatively high affinity for cardiac beta1-adrenoceptors. The authors speculate that it is worthy investigating whether these chemicals are useful in the management of vasospasm of aneurysmal subarachnoid hemorrhage.
Key Words: Tetrahydroisoquinoline; Inotropic action; Vasodilatation; Rat; Adrenoceptor; Vasospasm; Subarachnoid hemorrhage
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