Table 4.
Preclinical drug testing studies in the chronic models
| Drug | Protocol | Drug effect | References |
|---|---|---|---|
| Multiple-hit rat model (treatments tested after onset of spasms) | |||
| ACTH1–24 | 0.0125 mg/kg/day i.p., PN4–13 | No effect on spasms | Scantlebury et al. 2010 |
| Vigabatrin (GABA aminotransferase inactivator) | 10–20 mg/kg i.p. twice daily, starting on PN4 | Transient suppression of spasms on PN5; higher doses were not tolerated | Scantlebury et al. 2010 |
| CPP-115 (high affinity vigabatrin analog)a | Single or daily administration, starting on PN4; 0.1–1 mg/kg i.p. | Reduces spasms (PN5–7), no effect on learning or neurodevelopmental milestones, good tolerability Rapid onset effect on spasms on PN6–7 |
Briggs et al. 2014 |
| Phenytoin | Single injection (PN4); 20–50 mg/kg i.p. | No effect on spasms | Ono et al. 2011 |
| Rapamycin (mTOR inhibitor) | 1–3 mg/kg i.p. (PN4–12) Pulse protocol (i.p.): PN4: 6 mg/kg; PN5: 3 mg/kg; PN6: 3 mg/kg |
No acute but delayed effect on spasms only Rapid-onset reduction of spasms; stops spasms and improves Barnes maze performance (PN16–19) No effect on other seizures until PN20 Transient loss of weight during treatment period |
Raffo et al. 2011 |
| Carisbamatea | Single injection (PN4 or PN6–7); 30–60 mg/kg i.p. | Acute suppression of spasms | Ono et al. 2011 |
| NAX 5055 (galanin receptor 1 preferring agonist) | Single injection (PN4); 0.5–4 mg/kg i.p. | No effect on spasms; low expression of Galanin receptor 1 | Jequier Gygax et al. 2014 |
| ARX KI mouse model (treatment tested before onset of spasms) | |||
| Estradiol | 40 ng/g s.c., PN3–10 | Prevents spasms and epilepsy, restores interneuronal population in cerebral cortex PN33–40 treatment has no effect |
Olivetti et al. 2014 |
From Galanopoulou and Moshé 2015; modified, with permission, from Elsevier.
ACTH, adrenocorticotropic hormone; i.p., intraperitoneal; s.c., subcutaneous; PN, postnatal day; GABA, γ-aminobutyric acid; CPP-115, Catalyst Pharmaceutical Partners, Coral Gables, FL; mTOR, mammalian target of rapamycin.
aThese drugs have acquired orphan drug indication for infantile spasms by the Federal Drug Administration (FDA).