Dataset Information

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

ABSTRACT: We measured the affinity of five molecular container compounds (calabadions 1 and 2, CB[7], sulfocalix[4]arene, and HP-?-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.

SUBMITTER: Ganapati S

PROVIDER: S-EPMC5570556 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Ganapati Shweta S Grabitz Stephanie D SD Murkli Steven S Scheffenbichler Flora F Rudolph Maíra I MI Zavalij Peter Y PY Eikermann Matthias M Isaacs Lyle L

Chembiochem : a European journal of chemical biology 20170712 16

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 ...[more]

PMID: 28586110

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Project description:In summary, we characterized genomic signatures of response to drugs of abuse and we found positive correlations between the drug-induced expression and various behavioral effects. These signatures are formed by two dynamically inducible transcriptional networks: (1) CREB/SRF-dependent gene pattern that appears to be related to drug-induced neuronal activity, (2) the pattern of genes controlled at least in part via release of glucocorticoids and androgens that are associated with rewarding and harmful drug effects. The discovery of co-expressed networks of genes allowed for the identification of master-switch controlling factors involved in molecular response to the drugs. Finally, using the pharmacological tools we were able to dissect and inhibit particular gene expression patterns from genomic profile. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Addiction, Drugs of abuse, Time-course, Immediate Early Genes, Glucocorticoid receptor dependent genes, Cocaine, Heroin, Nicotine, Ethanol, Morphine, Methamphetamine The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Six the most addictive and harming drugs of abuse (morphine 20 mg/kg, heroin 10 mg/kg, ethanol 2 g/kg, nicotine 1 mg/kg, methamphetamine 2 mg/kg or cocaine 25 mg/kg, i.p.) were selected for the comparison. Drug doses were previously reported as rewarding in mice and further tested in our laboratory. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naïve animals were prepared for each time point. Design of the experiment assumed pooling of two animals per each array and using of three independent arrays per group. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches. 'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.

Dataset Information

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

Publications

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

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