새로운 Thebaine 유도체의 Opioid 수용체 결합과 활성에 관한 연구 = Opioid receptor binding and opioidergic activity of newly syntyesized the baine derivatives

다국어 초록 (Multilingual Abstract)

The primary purpose of the present study was to develop the novel centrally-acting analgesic drugs from novel thebaine drivarives. The receptor binding affinity/selectivity of 3 novel thebaine drivarives. The receptor binding affinity/selectivity of 3 novel thebaine derivative, C_19-(phenylic) thebinol(PTBL), N(4 nitrobenyzl)-C_14-trifluoromethyl carbinolic codinone(NBTFCC) and C_14-trifluoromethyl cabnolic morphine(TFMCM) was determined by employing type-selective radiolabelled ligands for μ-, δ-, or κ-opioid receptor, [^3H][D-Ala^2,N-Me-Phe^4,Gly-ol^3]-enkephalin (DAMGO), [^3H]naltrindole [NTI] or [^3H]U69593. Also, the opiodergic activity was examined in smooth muscle preparations, guine-pig ileum and mouse vas deferens.
In opioid receptor binding assay, TFMCM showed high affinity and selectivity to opioid μ-receptors. While PTBL and NBTFCC did not possess appreciable affinity to all three types of opioid receptors.
In guinea-pig ileal nerve-muscle preparations for examination of opioid μ-or κ-agonistic activity, all three thebaine derivatives, PTBL, NBTFCC, or TFMCM induced inhibition of electrically-evoked contraction. TFMCM showed most potent effect among those, and the receptor involved in this effect was considered to be opioid μ-receptors. We, also, used isolated mouse vas deferens to examine whether these thebaine derivatives posses agonistic property for opioid δ-receptors. All three thebaine derivatives showed low potency in inhibition of electricaly-driven contraction of mouse vas deferens.
These results shows that thebaine derivatives are promising candidates for te development of new centrally-acting analgesic drugs.