UCT is known around the world for its support of clinical pharmacologists and their studies as they look for the finest sorbents to perform the extractions. In a recent paper by Adam L. Halberstadt (Department of Psychiatry, University of California San Diego), UCT’s flagship sorbent Clean Screen® DAU (ZSDAU020) was employed in the study involving the interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine (Pharmacology, Biochemistry and Behavior (2016) 143 1–10).Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. It has been shown that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The present study was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation.
The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using ZSDAU020 columns which were conditioned by sequential addition of 3 mL of methanol, 3 mL of water, and 2 mL of 0.1 M phosphate (pH 6.0), and then the buffered samples were added. Next, the columns were sequentially washed with 3 mL of water and 3 mL of methanol. With care taken to prevent drying of the columns, the columns were eluted by the addition of 3 mL of 2% ammonium hydroxide in ethyl acetate and 4% ammonium hydroxide in methanol. After evaporation and reconstitution, the samples were analyzed by LC-MS/MS.
5-MeO-DMT (1 mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100,635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. This report confirms that 5-MeO-DMT can disrupt PPI by activating 5-HT2A, and indicate that MAOIs alter 5-MeO-DMT pharmacodynamics by increasing its accumulation in the central nervous system. This study demonstrates the importance of the extraction sorbent in the reproducibility of analyses when performed in clinical pharmacological assays and why analysts turn to UCT for the finest materials.