Table 1.

Representative compounds with affinity for sigma receptors.

Compounds	Ki (nM)
	σ	σ1	σ2
	SSRIs
Fluvoxamine[1]		36	8,439
Sertraline[1]		57	5,297
S(+)-Fluoxetine[1]		120	5,480
Citalopram[1]		292	5,410
Paroxetine[1]		1,893	22,870
TCAs
Opipramol[2]	50
Imipramine[1]		343	2,107
Desipramine[1]		1,987	11,430
MAOIs
Clorgyline[3]		2.9	505
(+)Deprenyl[3]		82	1,880
Harmaline[3]		310	2,100
Ro11-1163[3]		860	>50,000
Acetylcholinesterase inhibitor
Donepezil[4]a	14.6
Steroids
Progesterone[5]		24.6	15,700
Deoxycorticorsterone[6]	938
Dehydroepiandrosterone(DHEA)[7]	3,700
Sigma compounds
Haloperidol[8]		0.90	7.93
BD 1047[9]		0.93	9.15
NE-100[10]a		1.5	84.6
(+)Pentazocine[8]		1.62	728.4
SA4503[8]		4.63	63.09
(+)SKF 10,047[11]a		29	33,654
DTG[8]		35.45	39.87
Igmesine (JO1784)[12]a	39
UMB23[13]		41	32
OPC-14523[14]a		47	56
St. John’s Wort
Hyperforin[15]a	1,400
Hypericine[15]a	3,700

Note:

^adenotes IC₅₀ in nM. σ denotes affinity for sigma receptors where affinity at individual subtypes has not been reported.

^[1]Narita, N., K. Hashimoto, et al. (1996) “Interactions of selective serotonin reuptake inhibitors with subtypes of σ receptors in rat brain.” Eur J Pharmacol. 307: 117–119.

^[2]Rao, T.S., J.A. Cler et al. (1990) “Neurochemical characterization of dopaminergic effects opipramol, a potent sigma receptor ligand, in vivo.” Neuropharmacology 12: 1191–1197.

^[3]Itzhak, Y., I, Stein, et al. (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.

^[4]Kato, K., H. Hayako, et al. (1999). “TAK-147, an acetylcholinesterase inhibitor, increases choline acetyltransferase activity in cultured rat septal cholinergic neurons.” Neurosci Lett 260(1): 5–8.

^[5]McCann, D.J., A. D., Weissman et al., (1994) “Sigma-1 and sigma-2 sites in rat brain: comparison of regional, ontogenetic, and subcellular patterns.” Synapse 17 (3): 182–189.

^[6]Su, T.P., E.D. London et al., (1988) “Steroid binding at σ receptors suggests a link between endocrine, nervous, and immune systems” 240: 219–221.

^[7]Takebayashi, M.,T., Hayashi, et al. (2004) “A perspective on the new mechanism of antidepressants: neuritogenesis through sigma1 receptors.” Pharmacopsychiatry 37 Suppl 3: s208–S213.

^[8]Lever, J.R., J.L. Gustafson et al., (2006) “σ₁ and σ₂ receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503” Synapse 59: 350–358.

^[9]Matsumoto, R.R., W.D. Bowen et al., (1995) “Characterization of two novel σ receptor ligands: antidystonic effects in rats suggest σ receptor antagonism” Eur J Pharmacol 280: 301–310.

^[10]Nakazato, A., K, Ohta et al., (1999) “Design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine sigma ligands as potential antipsychotic drugs. J Med Chem 42(6): 1076–1087.

^[11]Bowen, W.D., B.R. de Costa et al. (1993) “[³H] –(+)-pentazocine: a potent and highly selective benzomorphan-based probe for sigma-1 receptors.” Mol Neuropharmacol 3: 117–126.

^[12]Earley, B., M., Burke et al., (1991) “Evidence for an anti-amnesic effect of JO 1784 in the rat: a potent and selective ligand for the sigma receptor.” Brain Res 546: 282–286.

^[13]Wang, J., A.L., Mack, et al, (2007) “Novel sigma (sigma) receptor agonists produce antidepressantlike effects in mice.” Eur. Neuropsychopharmacol., 17:708–716.

^[14]Tottori, K., T., Miwa, et al., (2001) “Antidepressant-like responses to the combined sigma and 5- HT_1A receptor agonist OPC-14523.” Neuropharmacology 41: 976–988.

^[15]Gobbi, M., M., Moia et al. (2001) “In vitro binding studies with two Hypericum Perforatum extractshyperforin, hypercin and biapigenin-on 5-HT₆, 5-HT₇, GABA_A/Benzodiazepine, sigma, NPY-Y₁/Y₂ receptors and dopamine transporters.” Pharmacopsychiatry 34 suppl 1:s45–s48.