Skimmianine and related furoquinolines function as antagonists of 5-hydroxytryptamine receptors in animals.
1. Skimmianine, kokusaginine and confusameline, three furoquinolines extracted from the leaves of Evodia merrillii (Rutaceae), were investigated to characterize their selective effects on subtypes of 5-hydroxytryptamine (5-HT) receptors. 2. In the isolated membranes of rat cerebrocortex, using [3H]-5-HT and [3H]-ketanserin as radioligands, skimmianine and the two other furoquinolines displaced radioligand bindings in a concentration-dependent manner. Lower concentrations were required to affect [3H]-ketanserin binding than [3H]-5-HT binding in the order skimmianine > kokusaginine > confusameline. 3. Furoquinolines inhibited 5-HT-induced contraction mediated by 5-HT2 receptors in the presence of methiothepin in rat isolated aorta. Also, the combination of furoquinolines with ketanserin showed an additive antagonism. 4. These furoquinolines were inactive on the 5-carboxamidotryptamine-induced relaxation of guinea-pig ileum, a 5-HT1-mediated event. However, 5-HT-induced contraction via 5-HT2 receptors was reduced by these furoquinolines in a way similar to that in blood vessels. 5. The failure of these compounds to affect the 5-HT-induced Bezold-Jarisch-like reflex in anaesthetized rats, the major 5-HT3-mediated action, ruled out an action on 5-HT3 receptors. 6. The results obtained suggest that three furoquinoline alkaloids may act on 5-HT receptors in animals, more selectively to the 5-HT2 subtype, in the order of skimmianine > kokusaginine > confusameline.
Cheng
J T
JT
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, Republic of China.
Chang
T K
TK
Chen
I S
IS
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D004365:Drugs, Chinese Herbal; D011804:Quinolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; C035932:skimmianine; D007650:Ketanserin