In-vivo metabolism in the rat and mouse of antrafenine to 1- m-trifluoromethylphenylpiperazine

Abstract

The analgesic antrafenine forms 1-m-trifluoromethylphenylpiperazine (mCF3PP) during its biotransformation in the rat and mouse. At least 14 and 3% of an antrafenine dose (25 mg kg-1 p.o.) reaches the systemic circulation as mCF3PP in the mouse and rat respectively. The metabolite easily enters the brain, reaching concentrations several times those in body fluids. This, together with the fact that mCF3PP is known to produce several pharmacological effects compatible with a stimulatory action on 5-hydroxytryptamine postsynaptic receptors, suggests that this metabolite may contribute to the parent drug's pharmacological effects.

New designer drug 1‐(3‐trifluoromethylphenyl) piperazine (TFMPP): gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry studies on its phase I and II metabolism and on its toxicological detection in rat urine

“…As possible pitfalls in the toxicological interpretation, it should be mentioned that TFMPP has been identified as a metabolite of antrafenine 66, 67. Furthermore, the TFMPP moiety can be found in other different drugs such as terciprazine and fluprazine 34.…”

Comparison of LC-MS and LC-DAD Methods of Detecting Abused Piperazine Designer Drugs

“…Some piperazine designer drugs may be found in biological fluids as metabolites of related therapeutic drugs. The phenylpiperazine derivative, TFMPP is a metabolism product of antrafenine, an analgesic and anti-inflammatory drug [ 17 , 53 ]. TFMPP, as an antrafenine metabolite, easily enters the brain, reaching concentrations higher than in body fluids, and has a stimulating effect on 5-HT receptors [ 21 , 53 ].…”

“…The phenylpiperazine derivative, TFMPP is a metabolism product of antrafenine, an analgesic and anti-inflammatory drug [ 17 , 53 ]. TFMPP, as an antrafenine metabolite, easily enters the brain, reaching concentrations higher than in body fluids, and has a stimulating effect on 5-HT receptors [ 21 , 53 ]. Most probably the TFMPP may contribute to the therapeutic drug’s pharmacological effects [ 53 ].…”

“…TFMPP, as an antrafenine metabolite, easily enters the brain, reaching concentrations higher than in body fluids, and has a stimulating effect on 5-HT receptors [ 21 , 53 ]. Most probably the TFMPP may contribute to the therapeutic drug’s pharmacological effects [ 53 ]. In addition, antrafenine used to reduce inflammatory and neuroinflammatory pain as a cyclooxygenase inhibitor, could be a drug with possible use in the treatment of the advanced respiratory disease COVID-19 [ 54 ].…”