Application of norketamine in preparation of antidepressant drug
A methylketamine, antidepressant technology, applied in the field of antidepressant drug treatment, can solve the problems of large difference, long delayed reaction time, limited duration of drug effect and the like
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Embodiment 1
[0028] Example 1 Behavioral experiment of LPS-induced mouse depression model
[0029] 1.1 Experimental animals
[0030] Male C57BL / 6J mice (C57 mice, 19-23 g, 8-10 weeks old) were selected. Before modeling, select male C57BL / 6J mice with appropriate aggressiveness, and start the formal modeling experiment after adapting to the SPF laboratory for 3-5 days. Before the experiment, the C57 mice were randomly divided into two groups: the control group (normal), the normal saline group (NS+LPS) and the norketamine group (norketamine+LPS) of different concentrations.
[0031] 1.2 Process of LPS-induced depression model in mice
[0032] The C57 mice were numbered, weighed, grouped, and given a single intraperitoneal injection of LPS (0.5 mg / kg), and 24 hours later were given normal saline and different concentrations of norketamine (5, 10, 20 mg / kg). 1h, 3h, 5h after administration, open field, tail flick and forced swimming experiments were performed.
[0033] 1.3 Depression-like...
Embodiment 2
[0042] Example 2 Contrasting the antidepressant effects of ketamine and norketamine
[0043]The C57 mice were numbered, weighed, grouped, and given a single intraperitoneal injection of LPS (0.5 mg / kg), and then given normal saline, ketamine (10 mg / kg) and norketamine (10 mg / kg) 24 hours later. 1h, 3h, 5h after administration, open field, tail flick and forced swimming experiments were performed. .
[0044] 2.1 Test method
[0045] 2.1 Depression-like behavioral experiment
[0046] Ditto.
[0047] 2.3 Experimental results
[0048] Experimental results: Figure 4 B shows that ketamine and norketamine have no significant effect on the total distance of movement in the open field test of LPS-induced depression mice; Figure 5 It shows that both ketamine and norketamine can reduce the immobility time in the tail flick test of LPS-induced depression mice, compared with NS group, **P Figure 6 It shows that both ketamine and norketamine can reduce the immobility time in LPS-ind...
Embodiment 3
[0050] Example 3 explores the mechanism of norketamine antidepressant
[0051] The C57 mice were numbered, weighed, grouped, and NS, ketamine, and norketamine (5, 10, 20 mg / kg) groups of different concentrations were injected intraperitoneally, and treated with LPS 30 minutes later, and TNF in serum was detected 90 minutes later - alpha concentration.
[0052] The results showed that the serum TNF-α concentration in depressed mice caused by LPS increased, and 10 mg / kg ketamine and 20 mg / kg norketamine could significantly reduce the serum TNF-α concentration ( Figure 7 ).
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