Abstract
Cebranopadol is known as a highly potent analgesic. Recent studies also demonstrated that administration of cebranopadol significantly decreased cocaine self-administration and significantly reduced cue-induced cocaine-seeking behaviors in rats. However, it was unclear whether these interesting behavioral observations are related to any potential effects of cebranopadol on cocaine pharmacokinetics or cocaine-induced hyperactivity. In principle, a promising therapeutic candidate for cocaine dependence treatment may alter the cocaine pharmacokinetics and/or attenuate cocaine-induced reward and hyperactivity and, thus, decrease cocaine self-administration and reduce cue-induced cocaine-seeking behaviors. In this study, we examined possible effects of cebranopadol on cocaine pharmacokinetics and cocaine-induced hyperactivity for the first time. According to our animal data in rats, cebranopadol did not significantly alter the pharmacokinetics of cocaine. According to our more extensive locomotor activity testing data, cebranopadol itself also dose-dependently induced hyperactivity in rats at doses higher than 50 µg/kg. Cebranopadol at a low dose of 25 µg/kg (p.o.) did not induce significant hyperactivity itself, but significantly potentiated cocaine-induced hyperactivity on Days 4 to 7 after the repeated daily dosing of the drug.
Highlights
Cebranopadol (CEB) is a novel, centrally acting analgesic which has been proven highly potent in various animal models of pain for preclinical studies and efficacious in multiple clinical trials[1]
We examined the possible effects of cebranopadol on cocaine pharmacokinetics and cocaine-induced hyperactivity
We carried out extensive locomotor activity tests to examine whether cebranopadol has any effects on the locomotor activity of rats with or without cocaine administration
Summary
Cebranopadol (CEB) is a novel, centrally acting analgesic which has been proven highly potent in various animal models of pain for preclinical studies and efficacious in multiple clinical trials[1]. A growing body of evidence suggests that simultaneous targeting of multiple opioid receptors is necessary to reduce classic opioid side effects[10,11,12] For this reason, with the characteristics of high activity at both the MOP and NOP receptors, along with multiple activation on other opioid receptors, cebranopadol has attracted much attention as a potential therapeutic candidate for treatment of cocaine dependence. A promising therapeutic candidate for cocaine dependence treatment may alter the pharmacokinetics (PK) of cocaine and/or attenuate cocaine-induced reward and hyperactivity (locomotor-stimulating effect)[15,16] and, decrease cocaine self-administration and reduce cue-induced cocaine-seeking behaviors. According to our more extensive locomotor activity testing data, cebranopadol itself dose-dependently induced hyperactivity in rats at doses higher than 50 μg/kg
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