Investigation of tetramezine excretion from rats

Abstract

The excretion of the novel antipsychotic agent tetramezine in rats was investigated using gas chromatography. Upon a single intramuscular administration in a dose of 200 mg/kg, only 5.2% of the introduced drug was recovered in the unchanged form, which implies that feces and urine are not the major routes of tetramezine excretion. The results suggest that tetramezine is well absorbed and the major proportion of it is subject to biotransformation, so that metabolism is the principal mechanism of clearance. The renal clearance (0.15 liter/(h × kg)) and half-elimination time (0. 37 h) for tetramezine in rats are determined using the experimental pharmacokinetic parameters (elimination constant and distribution volume).

Stereodynamics of tetramezine

“…Tetramezine [1,2‐bis(3,3‐dimethyldiaziridin‐1‐yl)ethane] shows antidepressant and dopamine‐positive activity1, 2 inhibiting the enzyme monoamineoxidase 3. Its bioavailability4 to dogs from intestine‐insoluble tablets, its pharmacokinetics5 and metabolization pathways6 in rats, and its excretion7 from rats have all recently been investigated by Prokopov et al Information about the stereochemical integrity of chiral drugs is of great importance, because, in the worst case, one of the stereoisomers can exhibit toxic effects8 and facile racemization makes stereoselective synthesis or separation obsolete 9–11. Therefore, the Food and Drug Administration explicitly requires the submission of unambiguous data concerning the configurational stability of chiral substances in new drug applications 12.…”

Stereodynamics of Small 1,2‐Dialkyldiaziridines

“…Many of the pioneering contributions to this field of research were made by Schmitz et al in the following decades. [4][5][6] Diaziridines show pronounced neurotropic activity, [7][8][9][10][11][12][13][14] and can be used in the synthesis of various heterocyclic compounds. 15 In these compounds, two chirotopic nitrogen atoms are present.…”