title: Nonimmobilizers and transitional compounds may produce convulsions by two mechanisms.
abstract: Some inhaled compounds cause convulsions. To better appreciate the physical basis for this property, we correlated the partial pressures that produced convulsions in rats with the lipophilicity (nonpolarity) and hydrophilicity (polarity) of 45 compounds: 3 n-alkanes, 18 n-haloalkanes, 3 halogenated aromatic compounds, 3 cycloalkanes and 3 halocycloalkanes, 13 halogenated ethers, and 2 noble gases (He and Ne). In most cases, convulsions were quantified by averaging the alveolar partial pressures just below the pressures that caused and slightly higher pressures that did cause clonic convulsions (ED50). The ED50 did not correlate with hydrophilicity (the saline/gas partition coefficient), nor was there an obvious correlation with molecular structure. For 80% of compounds (36 of 45), the ED50 correlated closely (r2 = 0.99) with lipophilicity (the olive oil/gas partition coefficient). Perhaps because they block the effect of GABA on GABA(A) receptors, five compounds were more potent than would be predicted from their lipophilicity. Conversely, four compounds may have been less potent than would be predicted because they (like conventional inhaled anesthetics) enhance the effect of GABA on GABA(A) receptors.
  
  
  CONCLUSIONS
  Nonimmobilizers and transitional compounds may produce convulsions by two mechanisms. One correlates with lipophilicity (nonpolarity), and the other correlates with an action on GABA(A) receptors.
authors: Department of Anesthesia, University of California, San Francisco 94143-0464, USA. edmond_eger@quickmail.ucsf.edu
authors: E I
authors: EI
authors: Eger
authors: D D
authors: DD
authors: Koblin
authors: J
authors: J
authors: Sonner
authors: D
authors: D
authors: Gong
authors: M J
authors: MJ
authors: Laster
authors: P
authors: P
authors: Ionescu
authors: M J
authors: MJ
authors: Halsey
authors: T
authors: T
authors: Hudlicky
mesh_terms: D000473:Alkanes / Q000737:chemistry / Q000633:toxicity; D018685:Anesthetics, Inhalation / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D003292:Convulsants / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry / Q000633:toxicity; D006844:Hydrocarbons, Cyclic / Q000737:chemistry / Q000633:toxicity; D006846:Hydrocarbons, Halogenated / Q000737:chemistry / Q000633:toxicity; D005741:Noble Gases / Q000737:chemistry; D000069463:Olive Oil; D010313:Partial Pressure; D010938:Plant Oils / Q000737:chemistry; D051381:Rats; D012640:Seizures / Q000139:chemically induced*; D012965:Sodium Chloride / Q000737:chemistry; D012995:Solubility
chemical_list: D000473:Alkanes; D018685:Anesthetics, Inhalation; D003292:Convulsants; D004987:Ethers; D006844:Hydrocarbons, Cyclic; D006846:Hydrocarbons, Halogenated; D005741:Noble Gases; D000069463:Olive Oil; D010938:Plant Oils; D012965:Sodium Chloride