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 (1 H 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.
Keywords:
calabadion; drugs of abuse; methamphetamine; molecular container; reversal agent.
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
MeSH terms
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2-Hydroxypropyl-beta-cyclodextrin / chemistry
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2-Hydroxypropyl-beta-cyclodextrin / pharmacology
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Animals
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Bridged-Ring Compounds / chemistry
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Bridged-Ring Compounds / pharmacology
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Calixarenes / chemistry
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Calixarenes / pharmacology
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Crystallography, X-Ray
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Fentanyl / chemistry
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Heterocyclic Compounds, 4 or More Rings / chemistry
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Heterocyclic Compounds, 4 or More Rings / pharmacology*
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Illicit Drugs / chemistry
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Illicit Drugs / toxicity*
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Locomotion / drug effects*
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Male
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Methamphetamine / chemistry
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Methamphetamine / toxicity*
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Phenols / chemistry
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Phenols / pharmacology
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Rats, Sprague-Dawley
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Sequestering Agents / chemistry
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Sequestering Agents / pharmacology*
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Sulfonic Acids / chemistry
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Sulfonic Acids / pharmacology*
Substances
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Bridged-Ring Compounds
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Heterocyclic Compounds, 4 or More Rings
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Illicit Drugs
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Imidazoles
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Phenols
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Sequestering Agents
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Sulfonic Acids
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calabadion 1
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calabadion 2
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cucurbit(7)uril
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p-sulfonatocalix(4)arene
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Calixarenes
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2-Hydroxypropyl-beta-cyclodextrin
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Methamphetamine
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Fentanyl