Table 3.
Preclinical drug testing in models of epileptic spasms
| Acute models | NMDA model | Prenatal betamethasone/postnatal NMDA | Prenatal stress/postnatal NMDA | Down/GBL |
|---|---|---|---|---|
| ACTH1–24 | No effect on latency (0.1–0.4 mg/kg i.p.) (Velisek et al. 2007) | Shortens EDR (40, 80 µg/mouse) (Cortez et al. 2009) | ||
| ACTH1–39 (rat synthetic) | No effect on latency (0.1 mg/kg i.p.) (Velisek et al. 2007) | Delays spasms (0.1 mg/kg i.p.) (Velisek et al. 2007) | No effect with single dose; delay and reduction of spasms after nine doses (0.3 mg/kg/dose, three doses/day s.c.) (Yum et al. 2012) | |
| ACTH1–39 (porcine, natural) | Delays and reduces spasms severity (100 U/kg ACTH i.p.) (Wang et al. 2012) | No effect on EDR duration (20–80 µg/mouse) (Cortez et al. 2009) | ||
| Hydrocortisone | Increases spasms (10–25 mg/kg) (Kabova et al. 1999) | |||
| Methylprednisolone | Repetitive, but no single dose reduces spasms incidence (60 mg/kg) (Chachua et al. 2011) | |||
| Vigabatrin | Decreased spasms incidence (600–1200 mg/kg) (Kubova and Mares 2010) | Decreases spasms incidence (250 mg/kg) (Chachua et al. 2011) | Shortens EDR (250–500 mg/kg) (Cortez et al. 2009) | |
| Pyridoxine (B6) | Decreases spasms incidence; induces epileptiform activity (250 mg/kg) (Kabova et al. 1999) | |||
| Clonazepam | No effect (0.2–1 mg/kg) (Velisek and Mares 1995) | |||
| Valproic acid | No effect (100–400 mg/kg) (Kubova and Mares 2010) Modest effect (Kabova et al. 1999) |
Shortens EDR (100–400 mg/kg) (Cortez et al. 2009) | ||
| Ethosuximide | Shortens EDR (25–50 mg/kg) (Cortez et al. 2009) | |||
| CGP 35348 | Shortens EDR (50–200 mg/kg) (Cortez et al. 2009) | |||
| Baclofen | Prolongs EDR (0.5–2 mg/kg) (Cortez et al. 2009) | |||
| 5-Hydroxy-tryptophan | Prolongs EDR (100–150 mg/kg) (Cortez et al. 2009) | |||
| Rapamycin | No acute effect with low doses (3 mg/kg i.p.) (Chachua et al. 2011) |
From Galanopoulou 2013; modified, with permission.
Baclofen, GABAB receptor agonist; CGP 35348, GABAB receptor antagonist; GBL, γ-butyrolactone; EDR, electrodecremental response; i.p., intraperitoneally; s.c., subcutaneously; U, units; ACTH, adrenocorticotropic hormone; NMDA, N-methyl-d-aspartate.