Muralikrishnan DhanasekaranMOHAMMED HAMED MOHAMMED ALMAGHRABI2022-06-022022-06-02https://drepo.sdl.edu.sa/handle/20.500.14154/61110New or novel Psychoactive substances (NPS) or designer drugs are often uncontrolled synthetic chemicals that are analogs to classic controlled substances and have been a public health threat in the last two decades. The rapid expansion in manufacturing and trafficking of NPS is an alarmingly significant challenge to global health. It has led to drastic abuse, especially among young people. Due to relatively limited information regarding the analytical characteristics, pharmacokinetic, pharmacodynamic, and toxicological profile, there is a need for pertinent research on these substances immediately. Many research areas are associated with NPS phenomena, such as forensic analysis, neuropharmacology, epidemiology, toxicology, and prevention science. The first step to face this issue is the identification and detection of these kinds of substances. Forensic analysis of illicit drugs is a significant path to help in resolving this issue. One of the reasons that facilitate the spread of NPS is the simplicity of designing these kinds of substances. In addition, the availability of chemical precursors can produce uncountable regioisomers related to controlled substances. Designer piperazine drugs are a novel class of NPS that has been introduced in the market of illicit drugs in 2000 and known as party pills. The most used recreational drugs in the piperazine class are benzylpiperazine (BZP) and 3-triflourmethylphenylpiperazine (3-TFMPP). These compounds are usually used in combination to mimic the psychostimulant effects of amphetamine and MDMA, but ten-fold less potent. In the current study, several piperazine derivatives have been designed and synthesized based on the structural elemental of BZP and 3-TFMPP. In addition to creating an analytical profile of each compound using the gas chromatography, mass spectometry, and infrared spectroscopy. Lastly, we also investigate the neuropharmacological profile of some novel piperazine derivatives and the mechanisms of action.en