Table 1.
Summary of in vivo effects of allosteric Sig1R modulators.
| Compound | Dose, mg/kg (route of administration) | Effect in vivo | Animal model (species) | Molecular target | References |
|---|---|---|---|---|---|
| Phenytoin* | 5–20 (i.p.) | Anti-seizure activity/*anti-epileptic drug | Maximal electroshock-induced seizures (mice) | Voltage-gated sodium channels | Jones et al., 1981; Reviewed in Tunnicliff, 1996 |
| 20, 40 (p.o.) | Anti-seizure activity | Ischemia-induced epilepsy (rats) | Edmonds et al., 1996 | ||
| Ropizine (SC-13504) |
2, 4 (i.v.) | Anti-seizure activity | Penicillin-induced epileptogenic foci (cats) | N/A | Edmonds and Stark, 1974 |
| 4, 6 (i.v.) | Anti-seizure activity | Photosensitive epilepsy (baboons) | Magnesium-dependent ATPase | Meldrum et al., 1976 | |
| 3, 300 (p.o.) | Anti-seizure activity | Partially kindled hippocampal seizures (rats) | N/A | Albertson et al., 1978 | |
| 2.5 (ED50) | Anti-seizure activity | Maximal electroshock-induced seizures (rats) | N/A | Edmonds et al., 1979 | |
| SKF-83959 | 0.5 (i.p.) | Anti-Parkinson activity | 6-OHDA-induced Parkinson's disease model (rats) | Dopamine D1 receptor | Zhang et al., 2007 |
| 0.5, 1 (i.p.) | 6-OHDA-induced Parkinson's disease model (rats) | Zhen et al., 2005 | |||
| 2, 4, 8 (i.p.) | Anti-depressant activity | Tail suspension test; forced swimming test (mice) | SERT/NET/DAT | Fang et al., 2013 | |
| 0.5, 1 (i.p., 10 days) | Chronic social defeat stress model (mice) | Dopamine D5 receptor | Jiang et al., 2015 | ||
| 10, 20, 40 (i.p.) | Anti-seizure activity | PTZ-induced seizures; kainic acid-induced status epilepticus (mice) | Sig1R | Guo et al., 2015 | |
| 1 (i.p., 11 days) | Anti-tumor activity | S.c. injection of GH3 and SCG7901 cancer cells (mice) | Dopamine D5 receptor | Leng et al., 2017 | |
| 0.5, 1 (i.p.) | Memory improvement | Scopolamine-induced learning deficits (mice) | Dopamine D1-D2 receptor heteromer | Sheng et al., 2018 | |
| SCH-23390 | 0.1–0.3 (i.p.) | Anti-seizure activity | Pilocarpine-induced seizures (rats) | Dopamine D1 receptor | Barone et al., 1992 |
| 0.8 (i.p.) | Pilocarpine-induced seizures (mice) | Burke et al., 1990 | |||
| 0.5 (i.p.) | Soman-induced seizures (guinea pigs) | Bourne et al., 2001 | |||
| SKF-38393 | 1, 5, 10 (s.c.) | Anti-seizure activity | PTZ-induced seizures (mice) | Dopamine D1 receptor | Ogren and Pakh, 1993 |
| 5 (i.p.) | Memory improvement | Maternal deprivation-induced memory deficiency (rats) | Dopamine D1 receptor | Lejeune et al., 2013 | |
| SOMCL-668 | 40 (i.p.) | Anti-seizure activity | PTZ-induced seizures; kainic acid-induced status epilepticus (mice) | Sig1R | Guo et al., 2015 |
| 10, 20 (i.p.) | Anti-depressant activity | Forced swimming test; tail suspension test; sucrose preference test (mice) | Sig1R | Wang et al., 2016 | |
| E1R | 1, 5, 10 (i.p.) | Memory improvement | Scopolamine-induced learning deficits (mice) | Sig1R | Zvejniece et al., 2014 |
| 10, 50 (i.p.) | Anti-seizure activity | PTZ- and BIC-induced seizures (mice) | Sig1R | Vavers et al., 2017 | |
| OZP002 | 10, 30 (i.p.) | Anti-depressant-like activity | Forced swimming test (mice) | Sig1R | Maurice et al., 2017 |
| 0.1, 0.3 (i.p.) | Anti-amnesic activity | Scopolamine-induced learning deficits; i.c.v. injection of amyloid Aß25−35 peptide; APPSwe mice (mice) | Sig1R | ||
| 0.7 (i.p.) | Neuroprotection | I.c.v. injection of amyloid Aß25−35 peptide (mice) | Sig1R | ||
| Fenfluramine (ZX008)* | 3 nmol (i.c.v.) | Anti-seizure activity | I.c.v. injection of NMDA (mice) | Serotonin 5-HT2A receptor, Sig1R | Rodríguez-Muñoz et al., 2018 |
| 0.3, 1 (i.p.) | Anti-amnesic effect | Dizocilpine-induced learning deficits (mice) | Sig1R | Maurice et al., 2018 | |
| 10, 30 (i.p.) | Anti-depressant-like activity | Forced swimming test (mice) | Serotonin 5-HT1A receptor, Sig1R | Maurice et al., 2018 |
*
Drug used in clinics;
i.v., intravenous; i.p., intraperitoneal; s.c., subcutaneous; i.c.v., intracerebroventricular; Sig1R, sigma-1 receptor.