[Azabutyron concentration in the blood plasma and the hemodynamic effects of the preparation]. / Kontsentratsiia azabutirona v plazme krovi i gemodinamicheskie éffekty preparata.

In patients presenting mitral and aortal valvular defects with contemplated valve prosthetics it was shown that after an intravenous administration of azabutyrone in a dose of 4 mg/kg the drug produced a hypotensive effect in the large circulation, reduced insignificantly the cardiac output, venous pressure and the total peripheral resistance, inducing, at the same time, a short-term rise of the heart rate. The drug forced down materially (by more than 50 per cent) the pulmonary artery pressure in patients with pulmonary hypertension. The azabutyrone effects were seen to continue for 30 minutes with its blood plasma concentration of 1.5--3.0 gamma/ml. A clearcut correlation between the plasma content and the effect of the drug could be noted only as concerns the hypotensive action of azabutyrone in the lesser circulation.

[Clinical pharmacokinetics of azabutyron, a new short-term action neuroleptic]. / Klinicheskaia farmakokinetika azabutirona--novogo neiroleptika kratkovremennogo deistviia.

Pharmacokinetics of azabutyron--a new Soviet-made neuroleptic was studied clinically without anesthesia and also during surgery against the background of deep and surface fluorothan anesthesia in conjunction with artificial nitrous oxide and oxygen ventilation of the lungs (2:1). After intravenous administration of the drug in a dose of 4 mg/kg its maximum concentration (about 8 gamma/ml) was recorded in 5 minutes and the amount eliminated during 2 hours of observation comprised 1--2 per cent of the dose introduced. In practically healthy individuals with no anesthesia the pharmacokinetics of azabutyron lies within the limits of a bicompartment pharmacokinetics model, while surface anesthesia, blood loss changes the pharmacokinetics of the drug to such an extent that is has to be described from the standpoint of the unicompartment model system.

[Metabolism of the neuroleptic azabutyrone in the human body]. / Metabolizm neiroleptika azabutirona v organizme cheloveka.

Thin-layer and gas chromatography, spectrophotometry and mass-spectrometry were employed in studying metabolism of the neuroleptic azabutyron in man. It was ascertained that azabutyron is eliminated from the human organism in 24 hours unchanged (10 per cent of the dose administered). The main ways of its metabolism are oxidative N-dealkylation, reduction of the carboxylic group in the molecule, N-oxidation and conjugation of the drug.

[Effect of azabutyrone and its analogs on catecholamine metabolism in the brains of rats]. / Vliianie azabutirona i ego analogov na obmen kateholaminov v mozge krys

The action of the neuroleptic azabutyrone and its analogues on the accumulation and disappearance of 3H-norepinephrine and 3H-dopamine was studied in test on rats by using 3H-thyrosine, a tagged precursor of catecholamines. Azabutyrone is shown to be capable to speed up the dopamine circulation rate, as well as that of norepinephrine in the brain of rats. By comparison with azabutyrone the diazabicyclodekanyl derivative produces a more marked effect on the criculation of amines. A further "weighting" of the diazabicyclic radical and also substitution of chlorine for the fluorine atom in the para-position of the phenyl ring of butyrophenone leads to weakening of this effect.

[Pharmacokinetic study of the neuroleptic, azabutyrone]. / Farmakokineticheskoe izuchenie neiroleptika, azabutirona.

By using gas-chromatographic and spectrophotometric assays and adopting pharmacokinetic models of various types the pharmacokinetics of the neuroleptic azabutyron in the plasms, bile, gastric juice and urine of rabbits and rats was studied. The maximum level of azabutyron in the plasma (27 gamma/ml) was recorded 5 minutes after introduction of the drug. The amount of unchanged azabutyron passed with urine comprises 2--4 pc of the dose actually introduced, while the quantity of the agent excreted together with the bile and gastric juice was below 1 pc. The results thus obtained were subjected to electronic data processing according to the two-compartment pharmacokinetic model. It is presumed that in order to properly explain the pharmacokinetics of azabutyron some models of a greater complexity have to be used.

[Kinetics of the distribution of azabutyrone in the organism of rats]. / Kinentika raspredeleniia v organizme krys azabutirona

Spectrophotometry was employed in enquiring into the pharmacokinetics of azabutyrone in the organs of rats. With its intravenous or peroral administration the drug was found to quickly penetrate the cerebral tissues of rats and to accumulate therein. A direct relation between the dosage, the azabutyrone concentration in the cerebral tissues and the duration of the antiphenamine effect was disclosed. The cataleptic action correlates well with the drug concentration in the brain. No correlation between the level of the drug in the brain and the intensity of thiopental sodium anesthesia is observed.