New psychoactive drugs are substances of new synthesis that have been designed to mimicking the psychotropic effect of traditional illicit drugs. The poor knowledge about these emerging drugs represents a serious problem for public health. Here we evaluated the pharmacological profile, the brain penetration and the motivational properties of the synthetic opioid 3,4-dichloro-N-{[1(dimethylamino)cyclohexyl]methyl}benzamide (AH-7921). At this time, no data are available concerning its pharmacokinetic profile and behavioral effects. To reach these goals independent groups of naïve male Wistar rats were used. The doses of AH-7921 to be tested were selected on the basis of the primary observation Irwin test. Pharmacokinetics of AH-7921 was evaluated by HPLC-MS/MS while rewarding properties of the drug were assessed in an unbiased conditioned place preference (CPP) paradigm. Pharmacokinetics studies found that Cmax was reached 30 min after treatment, either in plasma and brain with a brain-to-plasma ratio of ~20. Plasma and brain levels then declined with a similar t1/2 (~3 hours) whereas one of the metabolites (N-didesmethylated) showed a very slow elimination from brain tissue. CPP data demonstrate that like another opioid (morphine 6 mg/kg i.p.), AH-7921 10 mg/kg i.p., but not 1 and 3 mg/kg, induces preference for the drug-paired compartment. Taken together these data demonstrate that AH-7921 is a potent opioid-like drug eliciting positive motivational properties with highly risk of addiction related to the long lasting t1/2 of its metabolites.
Characterization of AH-7921, a synthetic designer opioid
Claudio Marcello Marzo;
2016-01-01
Abstract
New psychoactive drugs are substances of new synthesis that have been designed to mimicking the psychotropic effect of traditional illicit drugs. The poor knowledge about these emerging drugs represents a serious problem for public health. Here we evaluated the pharmacological profile, the brain penetration and the motivational properties of the synthetic opioid 3,4-dichloro-N-{[1(dimethylamino)cyclohexyl]methyl}benzamide (AH-7921). At this time, no data are available concerning its pharmacokinetic profile and behavioral effects. To reach these goals independent groups of naïve male Wistar rats were used. The doses of AH-7921 to be tested were selected on the basis of the primary observation Irwin test. Pharmacokinetics of AH-7921 was evaluated by HPLC-MS/MS while rewarding properties of the drug were assessed in an unbiased conditioned place preference (CPP) paradigm. Pharmacokinetics studies found that Cmax was reached 30 min after treatment, either in plasma and brain with a brain-to-plasma ratio of ~20. Plasma and brain levels then declined with a similar t1/2 (~3 hours) whereas one of the metabolites (N-didesmethylated) showed a very slow elimination from brain tissue. CPP data demonstrate that like another opioid (morphine 6 mg/kg i.p.), AH-7921 10 mg/kg i.p., but not 1 and 3 mg/kg, induces preference for the drug-paired compartment. Taken together these data demonstrate that AH-7921 is a potent opioid-like drug eliciting positive motivational properties with highly risk of addiction related to the long lasting t1/2 of its metabolites.
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