Abstract:
:The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepam, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. All compounds were tested as the commercially available injectable preparation except for diazepam-lysine and loprazolam, which are not FDA approved. A peak effect time, as well as a dose to decrease performance time by 50% from control (PDD50), was determined. The calculated PDD50 (mumol/kg) values and peak effect times were midazolam, 1.16 at 15 min; loprazolam, 1.17 at 15 min; diazepam-lysine, 4.17 at 30 min; lorazepam, 4.98 at 15 min; diazepam, 5.27 at 15 min; phenobarbital, 101.49 at 45 min; chlordiazepoxide, 159.21 at 30 min; scopolamine, amitriptyline and acetazolamide did not demonstrate a performance decrement at any of the doses tested. The PDD50 values were compared with doses which have been utilized against nerve agent-induced convulsions or published ED50 values from standard anticonvulsant screening tests (maximal electroshock [MES] and subcutaneous pentylenetetrazol [scMET]). The results suggest that at anticonvulsant doses against nerve agents, all the benzodiazepines and phenobarbital have the potential to cause a performance decrement, whereas candidate anticonvulsants of the non-benzodiazepine or non-barbiturate type would not be expected to demonstrate this effect on motor performance. It is concluded that compounds such as acetazolamide, amitriptyline and scopolamine offer alternatives to the highly decrementing benzodiazepines and phenobarbital and should be further tested as anticonvulsant candidates against nerve agent intoxication.
journal_name
Drug Chem Toxicoljournal_title
Drug and chemical toxicologyauthors
Capacio BR,Harris LW,Anderson DR,Lennox WJ,Gales V,Dawson JSdoi
10.3109/01480549209014150subject
Has Abstractpub_date
1992-01-01 00:00:00pages
177-201issue
3eissn
0148-0545issn
1525-6014journal_volume
15pub_type
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