Anticonvulsant efficacy of drugs with cholinergic and/or glutamatergic antagonism microinfused into area tempestas of rats exposed to soman.
A group of antiparkinson drugs (benactyzine, biperiden, caramiphen, procyclidine, and trihexyphenidyl) has been shown to possess both anticholinergic and antiglutamatergic properties, making these agents very well suited as anticonvulsants against nerve agents. The first purpose of this study was to make a comparative assessment of the anticonvulsant potencies of the antiparkinson agents when microinfused (1 microl) into the seizure controlling area tempestas (AT) of rats 20 min before subcutaneous injection of soman (100 microg/kg). The second purpose was to determine whether cholinergic and/or glutamatergic antagonism was the effective property. The results showed that only procyclidine (6 microg) and caramiphen (10 microg) antagonized soman-induced seizures. Cholinergic, and not glutamatergic, antagonism was likely the active property, since atropine (100 microg), and scopolamine (1 microg) caused anticonvulsant effects, whereas MK-801 (1 microg), and ketamine (50 microg) did not. Soman (11 nmol) injected into AT resulted more frequently in clonic convulsions than full tonic-clonic convulsions. AT may serve as both a trigger site for soman-evoked seizures and a site for screening anticonvulsant potencies of future countermeasures.
Myhrer
Trond
T
Norwegian Defence Research Establishment, Protection Division, P.O. Box 25, 2027 Kjeller, Norway. trond.myhrer@ffi.no
Enger
Siri
S
Aas
Pål
P
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000187:drug effects*; D017470:Receptors, Glutamate / Q000187:drug effects*; D012999:Soman / Q000633:toxicity*
D000927:Anticonvulsants; D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D011950:Receptors, Cholinergic; D017470:Receptors, Glutamate; D012999:Soman
Brain Res. 2000 Aug 25;874(2):123-30
10960596
Epilepsia. 1988;29 Suppl 2:S15-34
2844521
Brain Res Bull. 1989 Jul-Aug;23(1-2):145-8
2553217
Eur J Pharmacol. 2005 Jun 15;516(3):227-34
15967427
Adv Clin Chem. 2004;38:151-216
15521192
Eur J Pharmacol. 1993 Feb 16;231(3):485-8
8449241
Neurosci Biobehav Rev. 1991 Fall;15(3):349-62
1683477
Neurotoxicology. 2002 May;23(1):7-17
12164550
Neurosci Biobehav Rev. 1993 Summer;17(2):203-15
8515903
J Biomed Sci. 1999 Mar-Apr;6(2):86-96
10087439
Epilepsia. 1991 Sep-Oct;32(5):604-15
1915166
Eur J Pharmacol. 2001 Oct 12;428(3):323-30
11689190
Exp Neurol. 1986 Sep;93(3):546-56
3743700
Brain Res. 1987 Dec 1;435(1-2):123-37
3427447
J Comp Neurol. 2001 Jun 4;434(3):289-307
11331530
Neurotoxicology. 1999 Aug;20(4):551-9
10499354
J Neurosci. 1998 May 15;18(10):3897-908
9570817
J Pharm Pharmacol. 1998 Nov;50(11):1299-305
9877318
J Pharmacol Exp Ther. 1995 Jul;274(1):353-60
7616420
Eur J Pharmacol. 1990 Sep 18;189(2-3):135-42
2253700
Basic Clin Pharmacol Toxicol. 2006 Feb;98(2):184-91
16445593
Neurosci Lett. 1992 May 11;139(1):104-7
1357600
Toxicol Appl Pharmacol. 2004 May 1;196(3):327-36
15094303
Nature. 1985 Oct 17-23;317(6038):623-5
4058572
Neurotoxicology. 2003 Jun;24(3):357-67
12782101
Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):249-53
7667336
Drug Chem Toxicol. 1984;7(6):605-24
6534735
Eur J Pharmacol. 2002 Aug 9;449(3):239-43
12167465
Acta Medica (Hradec Kralove). 2003;46(3):101-7
14677718
Neurosci Biobehav Rev. 1997 Sep;21(5):559-79
9353792
Epilepsy Res Suppl. 1996;11:17-43
9294726
J Pharmacol Exp Ther. 1988 Dec;247(3):1025-31
2849655
Arch Toxicol. 2006 Aug;80(8):502-7
16525814
Prog Drug Res. 2000;54:152-89
10857388
Toxicol Sci. 2003 Sep;75(1):108-16
12832655