Abstract
Opiate molecules, which shows the action of analgesia, sedation and euphoria, are major interest in classical opiate pharmacology. Opioid agonists and antagonists often have similar molecular structures, though they act differently. In this study, we have theoretically investigated the structures of opiate molecules by molecular orbital calculations. 25 opiate molecules are geometry optimized by semi-empirical AM1 calculations. Calculated molecules are morphine, oxymorphone, levorphanol, nalorphine, naloxone, levallorphan, heroin, codeine, etorphine, dihydromorphine, normorphine, pentazocine, apomorphine, buprenorphine, butorpahnol, dihydrocodeine, oxycodone, thebaine, bremazocine, cyclazocine, ketocyclazocine, naloxazone, naltrexazone, naltrexone, oxymorphazone. 25 molecules have common molecular skeleton that includes ten atoms(one nitrogen atom, one oxygen atom and 8 carbon atoms). We have obtained highest occupied molecular orbital(HOMO) for 25 molecules. Electron densities of HOMO on common ten atoms are used to perform multivariate statistical analysis. Though only 64% of HOMO densities of ketocyclazocine are localized on common ten atoms, all of the other 24 molecules have more than 75% localization of HOMO densities on common ten atoms. Principal component analysis using 10x25 data group is performed. Plot of scores of the first and the second principal component classified 25 molecules into three major groups. The first one includes only ketocyclazocine. The second one is constituted from 7 molecules. The third one is constituted from 17 molecules.
