Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Groups of atropinized dogs (6 dogs/group) were sedated, using xylazine HCl (2.2 mg/kg of body weight, IM) or acepromazine maleate (0.25 mg/kg, IM), and were anesthetized to loss of pedal reflexes, using thiopental, IV. The dogs were given 1 of the following test antagonists, IV: saline solution (2 ml; control group), 4-aminopyridine (4-AP; 0.5 mg/kg), yohimbine (0.4 mg/kg), doxapram (5.0 mg/kg), or dual combinations of the latter 3 substances in the same doses as used for each agent. In xylazine-treated dogs, the mean dosage of thiopental required to induce anesthesia was 4.8 mg/kg. Control mean arousal time (MAT) and walk time (MWT) were 37.1 minutes and 53.8 minutes, respectively. These values were decreased to less than 2 minutes and less than 3 minutes, respectively, by yohimbine, 4-AP + yohimbine, and doxapram + yohimbine. With doxapram and with 4-AP + doxapram, MAT was less than 2 minutes and MWT was less than 8 minutes. In acepromazine-treated dogs, the mean dosage of thiopental required for anesthesia was 15.0 mg/kg. Control MAT and MWT were 20.7 minutes and 36.5 minutes, respectively. These values were decreased to 8.1 minutes and 18.1 minutes, respectively, by doxapram, and to 3.5 minutes and 19.9 minutes, respectively, by doxapram + yohimbine. Doxapram, 4-AP + doxapram, and doxapram + yohimbine caused periodic extensor rigidity before and during arousal. This rigidity was accompanied by opisthotonos in 2 dogs of the doxapram + yohimbine group and may have been mild tonic seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversal of thiopental-induced anesthesia by 4-aminopyridine, yohimbine, and doxapram in dogs pretreated with xylazine or acepromazine. 286 16

The cerebral metabolic and circulatory effects of the two main classes of respiratory stimulants used in the apnea of the newborn and premature infant, i.e. methylxanthines and doxapram, have not been studied in great detail. In adult animals and humans, methylxanthines widely increase cerebral metabolic rates and simultaneously decrease cerebral blood flow levels. Thus, these compounds are able to reset the level of coupling between cerebral blood flow and energy metabolism inducing a relative hypoperfusion at a constant metabolic rate. In neonates, methylxanthines induce no change in cerebral blood flow as long as the drop in pCO2 related to drug administration is prevented. Information on doxapram effects on cerebral blood flow and metabolism is very scarse and limited to adult animals. Doxapram does not induce any change in cerebral energy metabolism and transiently decreases cerebral blood flow. In conclusion, it seems that the use of methylxanthines in apneic newborn infants fulfils a good margin of safety with respect to cerebral blood flow as long as no other pathology such as marked hypoxia or seizures is present. The use of doxapram also seems to stay in a good margin of safety in terms of cerebral blood flow and energy metabolism but many more studies are necessary to better understand the effects of this respiratory stimulant on cerebral functional activity.
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PMID:Effects of respiratory stimulants on cerebral metabolism and blood flow. 803 92

Sudden unexpected death in epilepsy (SUDEP) is a devastating event, and both DBA/1 and DBA/2 mice have been shown to be relevant animal models for studying SUDEP. DBA mice exhibit seizure-induced respiratory arrest (S-IRA), leading to cardiac arrest and subsequent sudden death after generalized audiogenic seizures (AGSs). This sequence of terminal events is also observed in the majority of witnessed human SUDEP cases. Several pathophysiological mechanisms, including respiratory/cardiac dysfunction, have been proposed to contribute to human SUDEP. Several (but not all) selective serotonin (5-HT) reuptake inhibitors (SSRIs), including fluoxetine, can reversibly block S-IRA, and abnormal expression of 5-HT receptors is found in the brainstem of DBA mice. DBA mice, which do not initially show S-IRA, exhibit S-IRA after treatment with a nonselective 5-HT antagonist. These studies suggest that abnormalities of 5-HT neurotransmission are involved in the pathogenesis of S-IRA in DBA mice. Serotonergic (5-HT) transmission plays an important role in normal respiration, and DBA mice exhibiting S-IRA can be resuscitated using a rodent ventilator. It is important and interesting to know if fluoxetine blocks S-IRA in DBA mice by enhancing respiratory ventilation. To test this, the effects of breathing stimulants, doxapram, and 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (PK-THPP) were compared with the effects of fluoxetine on S-IRA in DBA/1 mice. Although fluoxetine reduces the incidence of S-IRA in DBA/1 mice, as reported previously, the same dose of fluoxetine fails to enhance baseline respiratory ventilation in the absence of AGSs. Doxapram and PK-THPP augment the baseline ventilation in DBA/1 mice. However, these breathing stimulants are ineffective in preventing S-IRA in DBA/1 mice. These data suggest that fluoxetine blocks S-IRA in DBA/1 mice by cellular/molecular mechanisms other than enhancement of basal ventilation. Future research directions are also discussed. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
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PMID:Abnormalities of serotonergic neurotransmission in animal models of SUDEP. 2627 85