Interactions between Over-the-Counter and Illicit Drugs Utilizing Cytochrome P450 Metabolism: Potential for Exacerbation of Pharmacological Response.
CYP2D6 is the second largest drug metabolizer (20%) and is an important part of the phase I drug
metabolism, which transforms a functional group or adds a functional group to the drug to introduce or unmask polar bodies.4,5 The active catalytic site of CYP2D6 contains acidic amino acid residues (Asp301 and Glu216) and as such will bind substrates which contain basic nitrogen and planar aromatic ring groups.
Drug-drug interactions at the level of the hepatic CYP microsomal system (Phase I reactions) can result in unexpected and dangerous side effects. Interactions between drugs may also affect forensic/medical toxicological analysis and interpretation. OTC-related inhibition of MA or MDMA metabolism will result in the accumulation of the illicit drug leading to increased toxicity. The ability of X-ray crystallography to determine the CYP2D6 three-dimensional structure has aided significantly in understanding the mechanism of substrate activity at the CYP2D6 catalytic site.17 A sample schematic for the metabolism of MA, MDMA, CMT, and DEX (Figure 1) includes the primary metabolite for each of the parent compounds. At higher concentrations, recreational users reach dissociative effects similar to PCP or ketamine.
Poly-drug use is a growing concern due to the potential for drug-drug interactions and increased risk for severe drug-related toxicity. The current study addressed this question by using the
combination of the two scheduled drugs, MA (C-II) and MDMA (C-I), and two common and inexpensive OTC drugs, CMT and DEX. CYP2D6 is an important area of research due to the large
role it plays in metabolism, its genetic polymorphisms among humans, and its large number of substrates.
Toxicol Forensic Med Open J. 2017; 2(2): 51-62. doi: 10.17140/TFMOJ-2-120