Synthesis, antiulcer and antidepressive activity of 4-(4-halophenyl)-2-phenyl-1,2,3,4-tetrahydroisoquinolines.

4-(4-halophenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolines 2a-c have been synthesized by two methods and their biochemical and pharmacological properties have been studied. Biochemical investigations showed that all the compounds are strong inhibitors of DA, NE and 5-HT reuptake, the strongest effect being observed with compound 2b (R = Br). 2a-c exhibited a strong antiulcer activity on an experimental model of stress-induced ulcers with minimal doses (0.1 to 3.0 mg/kg), the effect of 2b being 30 times higher as compared to the H2-antagonist Ranitidin. At higher doses (10 to 30 mg/kg) 2b and 2c inhibited the Reserpinptosis. The most active compound in the reuptake inhibition 2b, expressed a high antidepressive activity in some other tests, comparable to that of the antidepressant Nomifensin. 2b has been selected for further pharmacological testing under the code name AN12.

[Correlations between the pharmacological effects of menilon and its concentrations in the plasma and brain of experimental animals]. / Korelatsii mezhdu niakoi farmakologichni efekti na preparata menilon i kontsentratsiite mu v plazma i mozuk na opitni zhivotni.

The authors carried out studies on the preparation menilon in order to establish eventual correlations between some pharmacological and pharmakokinetic indices. For this purpose they examined the activity of menilon in rats and mice during electric shock and hypothermia and determined the concentrations of the preparation in plasma and brain in rats. The obtained results from the pharmacological investigation revealed manifested action against the seizures after electric shock in both groups of animals. It was established as early as 30 minutes after oral administration of the preparation reached maximal activity after 1-2 hours and disappeared after 6 hours. The authors found strong and continuous hypothermic activity. The hypothermic effect of the doses used was preserved up to the end the 24 th hour. The lowering of temperature in rats was comparatively weaker and shorter. The pharmacokinetic studies showed quick oral resportion of menilon. It was found in plasma and brain of the experimental animals on the 30 th minite after its administration, reached maximal concentration between the first and second hour and still was established on the 24 th hour after administration. The maximal level of the preparation in plasma and brain after oral administration correlated well with the time of maximal activity of its antiseizure and hypothermic effects. The preparation menilon was comparatively slightly toxic.

[Determination of the plasma level and excretion to tempidon in man after oral use]. / Opredeliane na plazmeno nivo i ekskretsiia na tempidon u khora sled oralno prilozhenie.

Tempidone is original Bulgarian preparation, synthetized in NIHFI (Zelayskov Bikova). The plasma level of the preparation is determined after single oral administration in doses of 60 and 120 mg and for a period of five days in a dose of 20 mg three times daily per a person. It is shown that tempidone is quickly resorbed and is excreted unchanged mainly in urine. The preparation does not cumulate. The content of tempidone in plasma is determined by the method of thin-layer chromatography, but in urine-spectrophotometricaly.

[Effect of echinopsin and adepren on motor activity in rats]. / Vliianie na ekhinopsina i adeprena vurkhu dvigatelnata aktivnost na plukhove.

We have studied the influence of synthesized in NIHFI psychotropic drugs echinopsin and adepren for their locomotor activity on white rats in open field and staircase. Comparative parallel experiments were carried out with psychostimulants and antidepressive drugs utilized in therapeutic practice. We found that echinopsin in low doses increases the locomotor activity and in large doses decreases. Its action in open-field and staircase is different from the effect of amphetamine and coffeine which is confirmed by clinical evidence. Adepren decreases the locomotor activity in single application as a result of decreasing of brain noradrenaline which is similar to the effect of MAOI drugs.