چکیده (انگلیسی):

Four medical therapies previously shown to exert varying degrees of protection against
a convulsant dose of soman were assessed for potential behavioral side effects in a
novelty test. In Experiment 1, HI-6 (1-[([4-(aminocarbonyl)pyridino] methoxy)methyl]-2-
[(hydroxyimino)methyl]pyridinium) (125 mg/kg), scopolamine (1 mg/kg), physostigmine
(0.1 mg/kg), levetiracetam (50 mg/kg), and procyclidine (20 mg/kg) were tested separately.
In Experiment 2, the combination of HI-6, scopolamine, and physostigmine
(termed the physostigmine regimen) or HI-6, levetiracetam, and procyclidine (termed the
procyclidine regimen) were tested. In Experiment 3, the metabotropic glutamate modulators
DCG-IV ((2S,2R,3R)-2-(2,3-dicarboxycyclopropyl)glycine) (4 mg/kg) and MPEP
(2-Methyl-6-(phenylethynyl)pyridine hydrochloride) (30 mg/kg) were tested separately or
each drug in combination with HI-6 and procyclidine (termed the DCG-IV regimen and the
MPEP regimen, respectively). The results showed that the physostigmine and procyclidine
regimens both produced severe cognitive impairment (lack of preference for novelty) and
reduced locomotor and rearing activities. The DCG-IV and MPEP regimens caused milder
deficits on the same behavioral measures. Some relations were seen between prophylactic
capacity and degree of behavioral side effects. Only HI-6 or levetiracetam had no adverse
effects on behavior. DCG-IV or MPEP produced some impairment, whereas the detrimental
effects of scopolamine or procyclidine were pronounced. The relatively high dose of
procyclidine (anticholinergic and antiglutamatergic) needed for prophylactic efficacy may
have played a major role for the side effects of the regimens in which the drug was used. It
was concluded that behavioral side effects are inevitable for potent prophylactic therapies
against soman intoxication.