Neuropharmacological profile of MD 790501, a new benzamide derivative.

Using several classical screening procedures in different species MD 790501: (exo)-2,3 dimethoxy-N-[8-(phenylmethyl)-8-azabiocyclo [3.2.1]oct-3-yl] benzamide hydrochloride was shown to possess potent neuroleptic properties. The doses effective in the tests for neuroleptic activity were similar to or lower than those for heloperidol and clearly lower than those for bromopride, chlorpromazine, sulpiridie, sultopride and thioridazine. Compared with the reference compounds tested MD 790501 showed sedative, cataleptic and dyskinetic effects at doses relatively higher than those effective in tests for neuroleptic activity. MD 790501 possessed no noradrenolytic, anticholinergic, proconvulsant or anxiolytic activity. Its acute toxicity was in the same dose range as that of reference neuroleptics.

Neuropharmacological profile of MD 780515, a new reversible inhibitor of type A monoamine oxidase.

Using several classical screening procedures, MD 780515, 3-[[4-[5-(methoxymethyl)-2-oxo-3-oxazolidinyl]phenoxy]methyl]- benzonitrile, was shown to possess potential antidepressant activity consistent with preferential and short-acting inhibition of type A monoamine oxidase. The doses effective in the tests for antidepressant activity were much lower than the lethal doses and were similar to or lower than those for reference drugs. MD 780515 showed some anti-convulsant action but had little effect on spontaneous or conditioned behaviour and was devoid of anticholinergic activity.

Animal pharmacology of oxapadol (MD 720111), a new non-narcotic analgesic.

Oxapadol is a non-narcotic analgesic with an unusual chemical structure. It possesses analgesic activity in 4 species similar to that of other non-narcotic reference analgesics. It also shows antipyretic and antiinflammatory effects and in the analgesic dose range is devoid of undesirable neurological, gastro-intestinal and cardiovascular side-effects.

Use of Freund's adjuvant arthritis test in anti-flammatory drug screening in the rat: value of animal selection and preparation at the breeding center.

The Freund's adjuvant technic, using killed Mycobacterium butyricum suspended in mineral oil, is a refined tool for anti-inflammatory drug evaluation. Its use has long been reserved for testing and not for screening due to technical problems in the preparation of valid animal models. After reviewing the methodology, the authors demonstrated that the availability of arthritic rats from a modern breeding center (Charles River France, SA, Elbeuf, France) make the procedure applicable to drug screening. This has both practical and economic advantages. The animals can be used as test organisms for drug evaluation 14 da after treatment. Three criteria for measuring the effectiveness of anti-arthritic drugs have been established: an arithritic index determined by examination of the 4 paws; changes in the erythrocyte sedimentation rate; and changes in levels of plasma fibrinogen. The curative activity of test substances can be evaluated by a single series of measurements of these 3 criteria after 14 da of treatment. This test was compared with 2 others; edema of the paw induced by the subcutaneous injection of kaolin or carrageenan, and was found to be superior.