Evidence for involvement of amino acid neurotransmitters in anesthesia and naloxone induced reversal of respiratory paralysis.
General anesthetics render a person unconscious and may produce respiratory paralysis at therapeutic doses. No pharmacological agent is available to restore respiration and the mechanism/s of anesthesia or apnea is not clearly understood. In this report, we present evidence to show that naloxone reversed respiratory failure induced by thiopental, ketamine, halothane but not that induced by phenobarbital. Furthermore, 25 mg/kg, i.v. thiopental, 140 mg/kg, i.v. ketamine, and 3% halothane produced anesthesia without significantly altering respiratory rate, increased GABA and decreased glutamate (except ketamine and phenobarbital) levels in rat brain stem and cortex, but not in caudate and cerebellum. Aspartate, glycine and alanine levels were not affected in four brain regions studied. Pretreatment with TSC for 30 minutes did not change GABA or glutamate contents, but abolished the anesthetic as well as the respiratory depressant actions of the anesthetics. Increasing the doses of anesthetics produced respiratory failure with further rise in GABA and fall in glutamate in brain stem and cortex. Naloxone reversed respiratory paralysis and restored GABA close to control values in rat brain stem and cortex with no changes in caudate or cerebellum. Data presented here suggest that GABA may be necessary to produce loss of consciousness and naloxone reverses anesthetic induced respiratory failure.
Suria
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Department of Pharmacology, Faculty of Health Sciences, Aga Khan University Medical College, Karachi, Pakistan.
Rasheed
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F
D000758:Anesthesia; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D012133:Respiratory Paralysis / Q000139:chemically induced; D012663:Semicarbazides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000777:Anesthetics; D005971:Glutamates; D012663:Semicarbazides; D009270:Naloxone; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C005151:thiosemicarbazide