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

Autor: Ganapati S; Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA., Grabitz SD; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Murkli S; Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA., Scheffenbichler F; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Rudolph MI; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Zavalij PY; Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA., Eikermann M; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Isaacs L; Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2017 Aug 17; Vol. 18 (16), pp. 1583-1588. Date of Electronic Publication: 2017 Jul 12.
DOI: 10.1002/cbic.201700289
Abstrakt: 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.
(© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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