title: Serotonin and sudden death: differential effects of serotonergic drugs on seizure-induced respiratory arrest in DBA/1 mice.
abstract: In the DBA/1 mouse model of sudden unexpected death in epilepsy (SUDEP), administration of a selective serotonin (5-HT) reuptake inhibitor (SSRI), fluvoxamine, completely suppressed seizure-induced respiratory arrest (S-IRA) at 30 min after administration (i.p.) in a dose-related manner without blocking audiogenic seizures (AGSz), but another SSRI, paroxetine, reduced S-IRA but with a delayed (24 h) onset and significant toxicity. A serotonin-norepinephrine reuptake inhibitor, venlafaxine, reduced S-IRA incidence, but higher doses were ineffective. A selective 5-HT7 agonist, AS-19, was totally ineffective in reducing S-IRA. In developing DBA/1 mice that had not previously experienced AGSz, administration of a nonselective 5-HT antagonist, cyproheptadine, induced a significantly greater incidence of S-IRA than that of saline. This study confirms that certain drugs that enhance the activation of 5-HT receptors are able to prevent S-IRA, but not all serotonergic drugs are equally effective, which may be relevant to the potential use of these drugs for SUDEP prevention. Serotonergic antagonists may be problematic in patients with epilepsy.
authors: Departments of Pharmacology and Neurology and Division of Neurosurgery, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, USA. Electronic address: cfaingold@siumed.edu.
authors: Carl L
authors: CL
authors: Faingold
authors: Departments of Pharmacology and Neurology and Division of Neurosurgery, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, USA.
authors: Srinivasa P
authors: SP
authors: Kommajosyula
authors: Departments of Pharmacology and Neurology and Division of Neurosurgery, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, USA.
authors: X
authors: X
authors: Long
authors: Departments of Pharmacology and Neurology and Division of Neurosurgery, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, USA.
authors: Kristin
authors: K
authors: Plath
authors: Departments of Pharmacology and Neurology and Division of Neurosurgery, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, USA.
authors: Marcus
authors: M
authors: Randall
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use; D003533:Cyproheptadine / Q000009:adverse effects / Q000627:therapeutic use; D003645:Death, Sudden / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D020195:Epilepsy, Reflex / Q000503:physiopathology; D005260:Female; D006323:Heart Arrest / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012640:Seizures / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride
chemical_list: D018759:Adrenergic Uptake Inhibitors; D003511:Cyclohexanols; D003533:Cyproheptadine; D012701:Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride
keywords: Cyproheptadine; Fluvoxamine; Paroxetine; SNRI; SSRI; SUDEP; Serotonin; Venlafaxine