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. 2008 Dec;6(4):344–366. doi: 10.2174/157015908787386113

Table 1.

Pharmacology of some Usual σ1 Receptor Ligands

Compound Subtype Selectivity Affinity for σ1 Site* Function on σ1 Site Other Activities
Benzomorphans
(+)-Pentazocine σ1[61] +++ [61] Agonist [61] -
(–)-Pentazocine σ1/σ2[214] ++ [214] Agonist [31] κ1 agonist, µ1, µ2, ligand, low affinity δ, and κ3 opioid ligand [31]
(+)-SKF-10,047 σ1 [61] +++ [61] Agonist [61] NMDA receptor ligand [61]
Antipsychotics
Chlorpromazine σ1/σ2 [108] ++ [61] ? [61] Dopamine D2 antagonist [61]
Haloperidol σ1/σ2 [61] +++ [61] Antagonist [61] Dopamine D2 and D3 antagonist [75]; σ2 agonist [121]
Nemonapride σ1/σ2? [61] +++ [61] ? [61] Dopamine D2 antagonist [61]
Antidepressants
Clorgyline σ1 [74] +++ [74] Agonist? [9] Irreversible monoamine oxidase A inhibitor [74]
Fluoxetine σ1 [149] + [149] Agonist [61] Selective 5-HT reuptake inhibitor [149, 61]
Fluvoxamine σ1 [149] +++ [149] Agonist [61] Selective 5-HT reuptake inhibitor[149, 61]
Imipramine σ1 [149] ++ [149] Agonist [61] Monoamine reuptake inhibitor [61]
Sertraline σ1 [149] ++ [149] Agonist [9] Selective 5-HT reuptake inhibitor [149]
Antitussives
Carbetapentane σ1/σ2 [19] +++ [19] Agonist [121] Muscarinic antagonist [19]
Dextromethorphan σ1 [182] ++ [182] Agonist [121] NMDA receptor allosteric antagonist [93]
Dimemorfan σ1/σ2 [182] ++ [182] Agonist [182, 217] ?
Parkinson’s and/or Alzheimer’s disease
Amantadine ? + [162] Agonist? [162] NMDA antagonist, antiviral properties [25]
Donepezil σ1/σ2? [82] +++? [82] Agonist [126, 136,137] Cholinesterase inhibitor [82]
Memantine ? + [162] Agonist? [162] NMDA antagonist, antiviral properties [25]
Drugs of abuse
Cocaine σ1/σ2 [111] + [61, 111] Agonist [61] Monoamine transporters inhibitor, amongst other actions [175]
MDMA σ1/σ2[15] + [15] ? Preferential SERT inhibitor, among other actions [51]
Metamphetamine σ1/σ2 [151] + [151] ? Preferential DAT inhibitor, amongst other actions [45]
Putative endogenous ligands (neurosteroids)
DHEAS σ1 [61] + [61] Agonist [61] GABAA negative modulator [121]
Pregnenolone sulfate σ1 [61] + [61] Agonist [61] NMDA positive/GABAA negative modulator [121]
Progesterone σ1 [61] + [32, 33, 70] Antagonist [61] NMDA negative/GABAA positive modulator [121]
Anticonvulsants
Phenytoin (DPH) σ1 [214] Not applicable Allosteric Modulator [32, 33, 214] Delayed rectifier K+ channel blocker [152]; T-type Ca2+ current inhibitor [202]; Na+ current inhibitor [177]
Ropizine σ1 [214] Not applicable Allosteric modulator [214] ?
Other σ drugs
BD 737 σ1/σ2 [65] +++ [54] Agonist [54] -
BD 1008 σ1/σ2 [61] +++ [61] Antagonist [61] σ2 agonist? [120]
BD 1047 σ1 [107] +++ [107] Antagonist[107] α adrenoceptor ligand [107]
BD 1063 σ1 [107] +++ [107] Antagonist [107] -
BMY 14802 σ1/σ2 [108] ++ [108] Antagonist [54] 5-HT1A agonist [106]
DTG σ1/σ2 [61] +++ [61] ? [61] σ2 agonist [121]
Dup 734 σ1 [61] +++ [61] Antagonist [54] 5-HT2 antagonist [200]
Eliprodil (SL-82.0715) σ1/σ2 [56] ++ [56] ? [61] NMDA antagonist,α1 adrenoceptor ligand [56]
E-5842 σ1 [53] +++ [53] Antagonist [54] Low to moderate affinity for dopamine, 5-HT and glutamate receptors [53]
Haloperidol Metabolite I σ1 [108] ++ [34, 108] Antagonist [22] -
Haloperidol Metabolite II σ1/σ2 [108] +++ [34, 108] Irreversible antagonist [34] Dopamine D2 and D3 ligand [75]
4-IBP σ1/σ2[77] +++ [77] Agonist [9] Dopamine D2 ligand [77]
JO-1784 (Igmesine) σ1 [61] +++ [61] Agonist [61] -
Metaphit σ1/σ2 [11] ++ [34] Irreversible antagonist [11] Acylator of PCP and σ2 binding sites [11]
(+)-MR 200 σ1/σ2 [173] +++ [173] Antagonist [100] -
MS-377 σ1 [61] +++ [61] Antagonist [61] -
NE‑100 σ1 [61] +++ [61] Antagonist [61] -
OPC-14523 σ1/σ2 [61] +++ [61] Agonist [54] Agonist of pre- and post-synaptic 5-HT1A receptors [10]; SERT inhibitor [203]
Panamesine (EMD 57445) σ1/σ2? [61] +++? [61] Antagonist [54] One of its metabolites is a dopaminergic antagonist [61]
(+)-3-PPP σ1/σ2[64] ++ [32, 33] Agonist [61] σ2 agonist [121]; NMDA receptor ligand [68]; dopaminergic agonist [61]
PRE 084 σ1 [61] +++ [61] Agonist [61] -
Rimcazole (BW-234U) σ1/σ2[110] + [61] Antagonist [61] DAT inhibitor [110]
SA4503 σ1 [61] +++ [61] Agonist [61] -
SR 31742A ? +++ [61] ? High affinity for C8-C7 sterol isomerase [61]
*

Ki or KD values:

+++

< 50 nM;

++

< 500 nM;

+

< 10 µM.

?

: not studied or unclear at the moment.

-

: no other pharmacological target has been described.