A comparative conformational analysis of selected central nervous system stimulants

Thomas J. Sull, Gregory A. Chass, Andras Varro, Julius Gy Papp

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Amphetamines are a class of drugs that can have remarkable effects on the central nervous system. They all affect the adrenergic, dopaminergic, and serotonergic systems. Ephedrine and norephedrine are very structurally similar to amphetamine and methamphetamine, respectively, and also have similar, yet reduced effects on the central nervous system. As well, the N-methylated versions of amphetamines have greater pharmacological effects. This study examined and compared the conformations of amphetamine, methamphetamine, norephedrine, and ephedrine. Calculations were carried out at an RHF/3-21G level of theory. The lowest energy conformations of amphetamine and methamphetamine were found to be very similar. Those of norephedrine and ephedrine were also alike, as in the case of the two previously mentioned drugs, but, the lowest energy conformations of ephedrine and norephedrine compared to those of amphetamine and methamphetamine are not. The difference in thermodynamic stability between the lowest energy conformation of (+)-amphetamine-(g+, g+) - and the comparable minimum of (-)-norephedrine - (g+, g+, g-) - is 6.92 kcal mol-1. The difference found between (+)-methamphetamine - (g+, g+, a) - and (-)-ephedrine - (g+, g+, a, g-) - was 6.46 kcal mol-1. This difference may be a factor in the dissimilarity of potencies among the four drugs.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
JournalJournal of Molecular Structure: THEOCHEM
Volume623
Issue number1-3
DOIs
Publication statusPublished - Apr 4 2003

Keywords

  • Ab initio
  • Amphetamine
  • Computational analysis
  • Conformation
  • Ephedrine
  • Methamphetamine
  • Norephedrine

ASJC Scopus subject areas

  • Biochemistry
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

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