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Seizure Protection By Intrapulmonary Delivery Of Midazolam In Mice, Ashish Dhir, Dorota Zolkowska, Michael A. Rogawski
Seizure Protection By Intrapulmonary Delivery Of Midazolam In Mice, Ashish Dhir, Dorota Zolkowska, Michael A. Rogawski
Michael A. Rogawski
The lung provides a portal of entry that could be used to rapidly deliver anticonvulsant substances to the brain to treat seizures. In the present study, we demonstrate that midazolam, a water-soluble anticonvulsant benzodiazepine, confers potent seizure protection when administered via the intrapulmonary route. High dose (100 mg/kg) intraperitoneal midazolam induced loss-of-righting reflex in mice. Lower doses of midazolam (100–1000 μg/kg) when administered intraperitoneally did not induce loss-of-righting reflex but protected animals against pentylenetetrazol (PTZ)-induced seizures. Intrapulmonary administration of midazolam via a tracheal cannula protected against intraperitoneal PTZ seizures at lower doses. The minimal intraperitoneal and intravenous doses of midazolam …
Role Of Neurosteroids In The Anticonvulsant Activity Of Midazolam, Ashish Dhir, Michael A. Rogawski
Role Of Neurosteroids In The Anticonvulsant Activity Of Midazolam, Ashish Dhir, Michael A. Rogawski
Michael A. Rogawski
BACKGROUND AND PURPOSE Midazolam is a short-acting benzodiazepine that is widely used as an intravenous sedative and anticonvulsant. Besides interacting with the benzodiazepine site associated with GABA-A receptors, some benzodiazepines act as agonists of translocator protein (18 kDa) (TSPO) to enhance the synthesis of steroids, including neurosteroids with positive modulatory actions on GABA-A receptors. We sought to determine if neurosteroidogenesis induced by midazolam contributes to its anticonvulsant action. EXPERIMENTAL APPROACH Mice were pretreated with neurosteroid synthesis inhibitors and potentiators followed by midazolam or clonazepam, a weak TSPO ligand. Anticonvulsant activity was assessed with the intravenous pentylenetetrazol (PTZ) threshold test. KEY …