Experimental evaluation of bioavailability of tetramezine from tablets

Abstract

The absolute bioavailability f of the new antipsychotic drug tetramezine from tablets with intestine-soluble shell upon peroral administration in dogs amounted to 65.4% and was significantly higher than upon administration in the form of an aqueous solution of the parent substance (f = 48.1%). Comparative data on the peroral administration of the aqueous solution of tetramezine in dogs and rats showed that the bioavailability of tetramezine in dogs (48.1%) was much higher than that in rats (10%). The higher bioavailability of tetramezine from tablets is due to the intestine-soluble shell, which prevents the premature biotransformation of the drug in the acid medium of the stomach.

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.…”