Is the Analgesic Activity of Epibatidine Caused by a Chemical Reaction with the Morphine Opioid Receptor?
作者:
W. Brandt,
A. Barth,
期刊:
SAR and QSAR in Environmental Research
(Taylor Available online 1993)
卷期:
Volume 1,
issue 4
页码: 345-348
ISSN:1062-936X
年代: 1993
DOI:10.1080/10629369308029896
出版商: Taylor & Francis Group
关键词: epibatidine;conformation;opioid receptor;molecular modeling
数据来源: Taylor
摘要:
Using the molecular modeling program SYBYL, a conformational analysis of epibatidine has been performed. Two pairs of stable conformations due to the rotational degree of freedom for the pyridine ring have been found. These conformations were compared with morphine regarding spatial arrangements as well as electronic aspects. A very close agreement between the essential receptor positions occurring in morphine and epibatidine could be demonstrated. The protonable nitrogen atom in epibatidine is in exactly the same spatial position as in morphine, if the pyridine ring and the phenolic ring of morphine were matched to each other. Interestingly, it is also apparent that the pyridine nitrogen atom is in a close position to the bridging oxygen atom of morphine. Furthermore, the chlorine substituent fits very well with the hydroxyl group of morphine. A chemical reaction is postulated to permit epibatidine to function as an analgesic. The carbon-chlorine bond should be activated by the neighbourhood of the nitrogen atom in the pyridine ring and therefore undergo a chemical reaction resulting in formation of a covalent bond, perhaps of an oxygen bridge between the opioid receptor and epibatidine.
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