Molecular Containers Bind Drugs of Abuse in Vitro and Reverse the Hyperlocomotive Effect of Methamphetamine in Rats

Shweta Ganapati, Stephanie D. Grabitz, Steven Murkli, Flora Scheffenbichler, Maíra I. Rudolph, Peter Y. Zavalij, Matthias Eikermann, Lyle Isaacs

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

We measured the affinity of five molecular container compounds (calabadions 1 and 2, CB[7], sulfocalix[4]arene, and HP-β-CD) toward seven drugs of abuse in homogenous aqueous solution at physiological pH by various methods (1H NMR, UV/Vis, isothermal titration calorimetry [ITC]) and found binding constants (Ka values) spanning from <102 to >108 m−1. We also report X-ray crystal structures of CB[7]⋅methamphetamine and 1⋅methamphetamine. We found that 2, but not CB[7], was able to ameliorate the hyperlocomotive activity of rats treated with methamphetamine. The bioavailability of the calabadions and their convergent building block synthesis suggest potential for further structural optimization as reversal agents for intoxication with nonopioid drugs of abuse for which no treatments are currently available.

Original languageEnglish (US)
Pages (from-to)1583-1588
Number of pages6
JournalChemBioChem
Volume18
Issue number16
DOIs
StatePublished - Aug 17 2017
Externally publishedYes

Keywords

  • calabadion
  • drugs of abuse
  • methamphetamine
  • molecular container
  • reversal agent

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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