Background: Designer Drugs are a group of psychoactive substances synthesized from chemicals to emulate the pharmacodynamic and pharmacokinetic actions of widely used substances of abuse.  A simple structural modification of the chemical structure can alter the pharmacodynamic and pharmacokinetic profile.  However, the in-silico properties (pharmacodynamics and pharmacokinetic) of New Psychoactive Substance / Designer Drugs are not well elucidated.

Aim: In this study, we assessed the possible pharmacodynamic and pharmacokinetic effects of Piperazine derivatives (2-TFMPP, 3-TFMPP, 4-TFMPP, 2-TFMBzPP, 3-TFMBzPP, 4-TFMBzPP and BZP) using Qikprop. 

Results and Discussion: Based on Lipinski’s rule of five, Jorgensen’s rule of three, QPlogBB and the QPPCaco, the TFMPP derivatives can undergo passive diffusion and can be highly absorbed after oral administration (can be bioactive orally).  TFMPP derivatives have lower cLogp, HBD and HBA values.  Therefore, these designer drugs can cross the BBB and possibly exhibit significant pharmacodynamic effects in the central nervous system. Furthermore, PISA and FOSA values can be used to correlate with the neurotoxicity of a drug / chemical. The structural changes can lead to increase in potency or toxicity of these designer drugs, making them even more stimulatory, addictive, and toxic than their parent compound (stimulants / drugs of abuse). However, there is a possibility that these designer drugs can become less toxic and still exhibit the required pharmacodynamic effects compared to the parent compounds.  Thus, the non-toxic designer drugs can exhibit potent therapeutic effects to treat various ailments in humans and veterinary purposes.