Pharmacological Profile of a New Psycho therapeutic Agent: 4-/7-Fluorophenyl-5-N(N’-o-methoxyphenyl)piperazinoethyl-4-oxazolin-2-one (LR 511)

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Abstract
LR 511 modified the spontaneous or specialized behavior of animals and antagonized some CNS effects evoked pharmacologically, thus sharing a number of properties with neuroleptics and thymoleptics but also revealing differences. At low doses (1-10 mg/kg p.o. [per os]), LR 511 greatly reduced the spontaneous and amphetamine-induced locomotor activity, showing peculiarly flat dose-response curves. Within the same dose range the compound was also able to reduce the aggressivity induced by isolation and the exploring activity in a new environment, to abolish the conditioned avoidance reflex and the conditioned food intake (.DELTA.W [weight change] test), to antagonize the stereotypy evoked by amphetamine, the emesis induced by apomorphine and the death caused by catecholamines. At higher doses (10-30 mg/kg p.o.), LR 511 inhibited apomorphine-induced gnawing, revealed anti-nociceptive activity and possessed tryptaminergic, histaminergic and serotoninergic blocking properties (while it lacked, even at much higher doses, central and peripheral anticholinergic and anticonvulsant properties). At very high doses (30-80 mg/kg p.o.), the compound potentiated some hypnotic drugs (while being completely devoid of hypnotic properties itself) and caused hypothermia and catalepsy. Inhibition of righting reflex and muscle relaxation were observed only with doses of LR 511 > 100 mg/kg p.o. The activity on the cardiovascular system was weak and very inconstant. Acute toxicity studies indicated that the drug was atoxic either in mice and rats up to the dose of 2000 mg/kg p.o., or in rabbits and dogs up to 1000 mg/kg p.o. Owing to its low toxicity and its strong psychotropic activity at very low dose levels, the therapeutic margin of safety of LR 511 appeared to be unusually great.