Vijayapandi Pandi, Nagappa Anantha Naik
Pharmacy Group, Birla Institute of Technology and Science, Rajasthan, India.
Yakugaku Zasshi. 2005 Aug;125(8):653-7. doi: 10.1248/yakushi.125.653.
The effects of losartan potassium, an angiotensin AT(1) receptor blocker on immobility in forced swim test have been studied. Effect of losartan potassium, nortriptyline HCl, fluoxetine HCl and reserpine per se and in combination on forced swimming-induced immobility in mice have also been studied. In mice, losartan potassium elicits biphasic responses i.e. positive responses at lower doses (0.1, 1.0 and 5 mg/kg, i.p.) in the forced swim test, a test of potential antidepressant activity and vice versa at higher dose (20 and 100 mg/kg, i.p.). In chronic studies, enhancement in immobility was observed for losartan potassium (3 and 30 mg/kg, p.o., 21 days). In acute combination studies, losartan potassium (1 and 5 mg/kg) significantly reversed the reserpine-induced immobility, but vice versa at 100 mg/kg. Losartan potassium (0.1 and 5 mg/kg) potentiate antidepressant activity of nortriptyline (30 mg/kg, i.p.) in mice, but vice versa at 100 mg/kg. Likewise, Losartan potassium (100 mg/kg), significantly reversed antidepressant activity of fluoxetine HCl, but at 0.1 and 5 mg/kg, failed to modify fluoxetine HCl induced immobility. The obtained biphasic effect of losartan potassium on immobility in mice might be due to inhibitory effect on AT(1) receptor at lower dose and pronounced effect on AT(2) receptor at higher dose (large concentrations of losartan potassium can displace Angiotensin II (Ang II) from its AT(1) receptor to AT(2) receptor.
研究了血管紧张素AT(1)受体阻滞剂氯沙坦钾对强迫游泳试验中不动时间的影响。还研究了氯沙坦钾、盐酸去甲替林、盐酸氟西汀和利血平本身及其组合对小鼠强迫游泳诱导的不动时间的影响。在小鼠中，氯沙坦钾引起双相反应，即在强迫游泳试验（一种潜在抗抑郁活性的试验）中，较低剂量（0.1、1.0和5mg/kg，腹腔注射）时出现阳性反应，而在较高剂量（20和100mg/kg，腹腔注射）时则相反。在慢性研究中，观察到氯沙坦钾（3和30mg/kg，口服，21天）使不动时间增加。在急性联合研究中，氯沙坦钾（1和5mg/kg）显著逆转利血平诱导的不动，但在100mg/kg时则相反。氯沙坦钾（0.1和5mg/kg）增强小鼠中盐酸去甲替林（30mg/kg，腹腔注射）的抗抑郁活性，但在100mg/kg时则相反。同样，氯沙坦钾（100mg/kg）显著逆转盐酸氟西汀的抗抑郁活性，但在0.1和5mg/kg时，未能改变盐酸氟西汀诱导的不动时间。氯沙坦钾对小鼠不动时间产生的双相效应可能是由于较低剂量时对AT(1)受体的抑制作用以及较高剂量时对AT(2)受体的显著作用（高浓度的氯沙坦钾可将血管紧张素II (Ang II) 从其AT(1)受体置换到AT(2)受体）。
