Sigma ligands

Akunne, H.C., Zoski, K.T., Whetzel, S.Z., Cordon, J.J. Neuropharmacological profile of a selective sigma ligand, igmesine a potential antidepressant and anti-stress actions. Neuropharmacology 41, 138-149, 2001. 

Sanchez, C., Papp, M. The selective sigma ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression. Behav. PharmacoL 11,117-124, 2000. 

Experimental evidence suggests that sigma receptors play an important role in regulating and integrating both immune and endocrine functions. In experimental studies, it has been shown that the selective sigma ligand N-allyl-normetazocine stimulates the hypothalamic-pituitary-adrenal axis... 

Renaudo A, Watry V, Chassot AA, Ponzio G, Ehrenfeld J, Soriani O (2004) Inhibition of tumor cell proliferation by sigma ligands is associated with K+ Channel inhibition and p27kipl accumulation. J Pharmacol Exp Ther 311 1105-1114... 

As part of our program to investigate the role of sigma-1 and -2 receptor subtypes, we focused our attention on the high affinity ethylenediamine sigma ligand 3 (Figure 1) and used it as a template [5]. 

Our interest in the development of sigma-2 selective ligands was spurred by evidence that this subtype may be responsible for the motor effects of sigma ligands (Bowen WD et al., personal communication). This is reinforced by the observation that DTG, which binds with lower affinity to sigma-1 receptors than (+)-pentazocine, is nonetheless more effective at causing motor disturbances in rats. 

Sigma ligand classes (18-4 7) discovered and developed from 1976-94 are illustrated in the Figures 3-6 below. The vast array of chemical diversity accommodated by sigma receptors suggests that these receptors may be primordial. This is reinforced by high densities of sigma receptors found in more primitive species such as reptiles (Matsumoto RR, personal communication). 

Several models have been proposed to account for the chemical diversity of sigma ligands ... 

Monnet, F.P., Debonnel, G., Bergeron, R., Gronier, B., de Montigny, C., 1994. The effects of sigma ligands and neuropeptide Y on N-methyl-D-aspartate-induced neuronal activation of CA3 dorsal hippocampus neurons are differentially affected by pertussin toxin. Br. J. Pharmacol. 112, 709-715. 

Booth, R.G., Baldessarini, R.J., 1991. (+ )-6,7-Benzomorphan sigma ligands stimulate dopamine synthesis in rat corpus striatum tissue. Brain Res. 557, 349-352. 

Chaki, S., Tanaka, M., Muramatsu, M., Otomo, S., 1994. NE-100, a novel potent sigma-ligand,preferentially binds to sigma(l) binding sites in guinea-pig brain. Eur. J. Pharmacol. 251, R1-R2. 

Itzhak, Y., Stein, I., Zhang, S.H., Kassim, C.O., Cristante, D., 1991. Binding of sigma-ligands to C57BL/6 mouse brain membranes effects of monoamine oxidase inhibitors and subcellular distribution studies suggest the existence of sigma-receptor subtypes. J. Pharmacol. Exp. Ther. 257, 141-148. 

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