Premium
Molecular Containers Bind Drugs of Abuse in Vitro and Reverse the Hyperlocomotive Effect of Methamphetamine in Rats
Author(s) -
Ganapati Shweta,
Grabitz Stephanie D.,
Murkli Steven,
Scheffenbichler Flora,
Rudolph Maíra I.,
Zavalij Peter Y.,
Eikermann Matthias,
Isaacs Lyle
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700289
Subject(s) - isothermal titration calorimetry , methamphetamine , bioavailability , chemistry , pharmacology , aqueous solution , in vitro , stereochemistry , combinatorial chemistry , biochemistry , medicine , organic chemistry
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 ( 1 H NMR, UV/Vis, isothermal titration calorimetry [ITC]) and found binding constants ( K a values) spanning from <10 2 to >10 8 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.