Skuza G, Rogóz Z
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Pol J Pharmacol. 1997 Sep-Oct;49(5):329-35.
As it is known, sigma receptor ligands have been able to modulate the central neurotransmitter systems, including noradrenergic-, NMDA-ergic- and dopaminergic ones, which are essential for the mechanism of action of antidepressant drugs. Therefore, it can be assumed that some selective sigma ligands can possess antidepressant-like activity. In the present studies 1,3-di-o-tolylguanidine (DTG), rimcazole (RIM) and EMD 57445 were examined in the forced swimming test in rats and mice. DTG and RIM decreased the immobility time in mice. EMD 57445 was inactive but it antagonized the anti-immobility effects of DTG and RIM. Both latter drugs did not change the locomotor activity of mice, EMD 57445 at higher dose decreased it. In addition, DTG showed antidepressant-like activity in rats, this effect being counteracted by EMD 57445. At the same time both drugs attenuated the spontaneous motor activity in rats. Taken together, the present results suggested that DTG and RIM may possess sigma agonistic activity while EMD 57445--the antagonistic one. Further investigations are needed to support agonistic/antagonistic activities of the studied sigma ligands and to elucidate the potential involvement of sigma site subtypes in this model.
众所周知，σ受体配体能够调节中枢神经递质系统，包括去甲肾上腺素能、N-甲基-D-天冬氨酸能和多巴胺能系统，这些系统对抗抑郁药物的作用机制至关重要。因此，可以推测一些选择性σ配体可能具有类抗抑郁活性。在本研究中，对1,3-二邻甲苯基胍（DTG）、利米唑（RIM）和EMD 57445进行了大鼠和小鼠的强迫游泳试验。DTG和RIM减少了小鼠的不动时间。EMD 57445无活性，但它拮抗了DTG和RIM的抗不动作用。后两种药物均未改变小鼠的运动活性，较高剂量的EMD 57445降低了小鼠的运动活性。此外，DTG在大鼠中显示出类抗抑郁活性，这种作用被EMD 57445抵消。同时，两种药物均减弱了大鼠的自发运动活性。综上所述，目前的结果表明DTG和RIM可能具有σ激动活性，而EMD 57445具有拮抗活性。需要进一步的研究来支持所研究的σ配体的激动/拮抗活性，并阐明σ位点亚型在该模型中的潜在参与情况。
