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The experiments outlined in this paper examined the effects of the novel antidepressant venlafaxine (VEN) (CAS 9930-78-4) in several behavioural and memory tests in comparison with the classic antidepressant imipramine (IMI) (CAS 113-52-0). The tests were carried out on male Wistar rats of about 200 g. The drugs were administered orally 30 min before the tests during 14 days. The aim of the locomotor activity test was to select the doses without influence on the motility of the animals and active at least in two behavioural tests. Such dose was 20 mg/kg b.w. for both drugs--VEN and IMI. In the immobility test, which reflects antidepressant drug activity, the following differences were found: VEN shortened immobility time (IT) on days 1 and 7 (no activity on day 14), whereas IMI shortened IT on days 7 and 14 and displayed no activity on day 1. In the two-compartment exploratory test both drugs displayed distinct anxiolytic effect on days 1 and 7, yet on day 14 only IMI was still active. In the maze test only VEN shortened food finding time on day 1, on day 7 and on day 14 during chronic treatment. IMI was inactive in the maze test. The authors conclude that the general pattern of VEN activity is similar to that of IMI, but in some tests, especially in the memory test, the new drug is superior to IMI.

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The behavioural effects of two antidepressants with opposite molecular mechanisms, tianeptine 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin - 11-yl)amino]heptanoic acid S,S-dioxide, CAS 66981-73-5) 5 mg/kg p.o., a serotonin reuptake enhancer, and fluoxetine (+/-)-N-methyl-3-phenyl-3-[(alpha, alpha, alpha-trifluoro-p- tolyl)oxy]propylamine, CAS 54910-89-3) 5 mg/kg p.o., a serotonin reuptake inhibitor, were compared after single and prolonged administration (7 and 14 days) once daily). In all experiments the drug effects were noted at the peak activity time: 30 min after tianeptine and 60 min after fluoxetine administration. In the immobility time test both drugs had a shortening effect on immobility time only after prolonged administration or, in single treatment, after joint administration. A different pattern was observed in the two compartment test: both antidepressants showed anxiolytic effects after single and prolonged treatment. However, when the drugs were given in joint administration, the anxiolytic effects were entirely abolished after single as well as prolonged treatment. In reference spatial memory test (food finding time in the maze) tianeptine had no effect, whereas fluoxetine caused, after single and prolonged treatment, a very marked improvement of reference memory. Joint administration of both drugs resulted in worsening the effects on memory in comparison to fluoxetine alone, but the results were still significantly better vs. control. In the test for sedative action (in the Activity Meter AM-1, where the movements of the animals are counted electronically) only after prolonged treatment with tianeptine a diminished locomotor activity could be observed. It is concluded that in the action of the drugs (beside the effect on serotonin uptake) other mechanisms must play an important role. The diminished locomotor activity after tianeptine suggests an influence on the dopaminergic or GABA-Receptor system.

To evaluate whether a relationship exists between insuessential hypertensive group compared with controls; in renovascular hypertensive patients 2 h after glucose linaemia (increased in essential hypertension) and endothelin level, we determined insulin and endothelinadministration the analogous difference was not statistically significant (P Ͻ 0.05 fasting; P Ͻ 0.01 after 1 h). 1-like (ET-1-Li) immunoreactivity in blood serum by radioimmunoassay (RIA) in essential (EH, n ‫؍‬ 64) andIn all the investigated groups the mean value of ET-1-Li immunoreactivity increased and decreased in parallel to renovascular (RVH, n ‫؍‬ 36) patients with hypertension and in healthy subjects (controls, n ‫؍‬ 44). The trials the changes in insulin concentration during the OGTT. The ET-1-Li level was positively correlated with insulin were carried out in fasting patients and after an oral glucose tolerance test (OGTT, 75 g). Each group of subjects concentration with a statistical significance for patients with essential hypertension 1 h after load (r ‫؍‬ 0.6578, P had similar body mass index (BMI) values. The mean values of insulin level were significantly (P Ͻ 0.0001 in Ͻ 0.05). The border of the significance level correlation was obtained in essential hypertensive patients 2 h after every case) elevated in patients with essential hypertension compared with renovascular and control subjects load (r ‫؍‬ 0.5227, P ‫؍‬ 0.06) and in controls 1 h after glucose administration (r ‫؍‬ 0.5465, P ‫؍‬ 0.054). Our results during the whole OGTT. There was no significant difference in insulin level between subjects with renovascular indicate a mutual connection between insulinaemia and an endothelin set; their relevance for the pathogenesis hypertension and controls. ET-1-Li immunoreactivity levels were significantly increased (P Ͻ 0.005 fasting; P of hypertension requires further research. Ͻ 0.01 after 1 and 2 h) throughout the whole test in the Keywords: insulin; endothelin; essential hypertension; renovascular hypertension to the fact that a particular relationship between ET