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Wray SR., Cowan A. 
“Correlation Between Animal and Clinical Findings with a Psychotomimetic Anticholinesterase.”. 
Neuropharmacology. 1973;12(4):397-400.
Abstract
The effect of RX-67668 (cis-2-phenyl-1-pyrrolidinocyclohex - ane HCl, Reckitt and Colman) a new reversible anticholinesterase on a discriminated avoidance test was investigated in rats Methods Female rats (200-220 g) were trained 5 days a week for 15 weeks on a Sidman discriminated avoidance schedule during which shocks were delivered every 10 sec unless a lever was Pressed before or during the shock-shock interval, In each session a 25 min period was allowed for a 'warm-up' followed by a 120 min trial, Drugs were given after the initial warm up, Control Sessions (saline) were held 24 hr before and 48 hr after each drug session. The following drugs were given to groups of 6 rats with 14 days'training between treatments: RX-67668 (1.0 or 10 mg/kg s.c.) physostigwine sulphate 0.5 mg/kg s.c., D-tartrate of LSD (lysergamide, Spofa), 0.5 mg/kg i.p. and pyridostigwine bromide (Mestinon, Roche) 0.5 mg/kg s.c. RX-67668 10 mg/kg physostėgmine and LSD all decreased avoidance but not escape responses. Neither 1.0 mg/kg RX-67668 nor pyridostigwine significantly altered responses. The response rate was scarcely altered by RX-67668 or LSD but physostigmine decreased it for 60 min after injection. The similarity between the actions of RX-67668, LSD and physostigmine on avoidance behaviour suggested that RX-67668 might have central effects. In an independent study in human volunteers 0.40-1 0 mg/kg i.v, RX-67668 has been shown to have psychotomimetic effects sufficient to withdraw the compound from use as a potential treatment for myasthenėa gravis, Discussion The extent to which inhibition of cholinesterase by RX-67668 per se causes the behavėoural disturbances is unknown.
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