Cromakalim, a Potassium Channel Opener, Ameliorates the Organophosphate and Carbamate-Induced Seizure in Mice.

Sattar Ostadhadi, Abouzar Moradi, Samira Zolfaghari, Vahid Nikoui, Ahmad Reza Dehpour
Author Information
  1. Sattar Ostadhadi: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  2. Abouzar Moradi: Department of Periodontics, School of Dentistry, Alborz University of Medical Sciences, Alborz, Iran.
  3. Samira Zolfaghari: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  4. Vahid Nikoui: Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
  5. Ahmad Reza Dehpour: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium channel openers including Cromakalim have been determined in previous studies. In the present experiment, the possible effect of Cromakalim on the convulsion and death induced by OPs and carbamates was studied in Mice. dichlorvos (an OP, 50 mg/kg) and physostigmine (a carbamate, 2 mg/kg) were used to induce seizure in animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg was injected 30 min before dichlorvos and physostigmine, and 5 min before glibenclamide (a potassium channel blocker, 1 mg/kg) administration. All injections were performed intraperitoneally. After drugs administration, the onset of convulsion, death, the severity of seizure, and rate of mortality were investigated. Results revealed that both dichlorvos and physostigmine induced seizure activity and lethality in 100% of the animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg significantly increased the latency of both seizure and death (P<0.05). Also, Cromakalim decreased the mortality rate induced by dichlorvos and physostigmine (P<0.05). On the other hand, glibenclamide blocked all aspects of the anticonvulsant effect of Cromakalim (P<0.05). This study revealed for the first time that Cromakalim (a KATP channel opener) diminishes the seizure and death induced by dichlorvos and physostigmine in Mice, and introduces a new aspect to manage the patients who suffer from OPs/carbamates-induced seizure.

Keywords

MeSH Term

Animals
Anticonvulsants
Carbamates
Cromakalim
Dichlorvos
Dose-Response Relationship, Drug
Glyburide
Male
Mice
Organophosphate Poisoning
Physostigmine
Potassium Channels
Seizures

Chemicals

Anticonvulsants
Carbamates
Potassium Channels
Cromakalim
Dichlorvos
Physostigmine
Glyburide

Word Cloud

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