Korean J Physiol Pharmacol.
1998 Jun;2(3):323-330.
Comparison of inodilator effect of higenamine, YS49, YS51, tetra-hydroisoquinoline analogs, and dobutamine in the rat
- Affiliations
-
- 1Department of Pharmacology, Cardiovascular Research Institute, College of Medicine, Gyeongsang National University, Chinju 660-280, Korea.
- 2Department of Chemistry, Sogang University, Seoul, Korea.
- 3Doping Control Center, Korea Institute of Science and Technology, Seoul, Korea.
- 4Natural Product Research Institute, Seoul National University, Seoul, Korea.
Abstract
- Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats' isolated atria and aorta. In addition, a (3H) prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have a-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 micrometer) in which pEC50 were 5.56-0.32 and 5.55+/-0.21, 5.99+/- 1.16 and 5.57+/-0.34, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs 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 and resulted in pA2 values of 8.07+/-0.84 and 7.93+/-0.11, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac beta-adrenoceptors. YS 49 YS 51, and higenamine showed alpha-adrenoceptor affinity in rat brain, in which the dissociation constant (Ki) was 2.75, 2.81, and 1.02 micrometer, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to alpha1-adrenoceptors in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac beta-adrenoceptors. Thus, these chemicals may be useful in the treatment of congestive heart failure.
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