Antiparkinson drugs used as prophylactics for nerve agents: studies of cognitive side effects in rats.
Antiparkinson agents possess excellent anticonvulsant properties against nerve agent-induced seizures by exerting both cholinergic and glutamatergic antagonisms. It is important, however, that drugs used as prophylactics not by themselves cause impairment of cognitive capability. The purpose of the present study was to make a comparative assessment of potential cognitive effects of benactyzine (0.3 mg/kg), biperiden (0.11 mg/kg), caramiphen (10 mg/kg), procyclidine (3 mg/kg), and trihexyphenidyl (0.12 mg/kg) separately and each in combination with physostigmine (0.1 mg/kg). The results showed that benactyzine, caramiphen, and trihexyphenidyl reduced rats' innate preference for novelty, whereas biperiden and procyclidine did not. When benactyzine, caramiphen, and trihexyphenidyl were combined with physostigmine the cognitive impairment disappeared. This counteracting effect, however, caused changes in locomotor and rearing activities not seen by each drug alone. Acetylcholinesterase inhibitors and anticholinergics used as prophylactics can offset each other, but exceptions are observed in a previous study when a very potent anticholinergic (scopolamine) or a high dose of procyclidine still results in cognitive deficits in spite of coadministration with physostigmine. Among the present drugs tested, procyclidine appears to be a robust anticonvulsant with few cognitive side effects.
Myhrer
Trond
T
Norwegian Defence Research Establishment, Protection Division, Kjeller, Norway. trond.myhrer@ffi.no
Enger
Siri
S
Aas
Pål
P
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001535:Benactyzine / Q000009:adverse effects; D001712:Biperiden / Q000009:adverse effects; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D003517:Cyclopentanes / Q000009:adverse effects; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity; D010830:Physostigmine / Q000009:adverse effects; D011352:Procyclidine / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D014282:Trihexyphenidyl / Q000009:adverse effects
D000978:Antiparkinson Agents; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D003517:Cyclopentanes; D009498:Neurotoxins; D009943:Organophosphorus Compounds; D001712:Biperiden; D001535:Benactyzine; D014282:Trihexyphenidyl; C004519:caramiphen; D010830:Physostigmine; D011352:Procyclidine