Pharmacology of 0-chlorobenzylidene malononitrile (CS)

1. The effects of o-chlorobenzylidene malononitrile (CS) have been studied on several isolated organs and tissues, anaesthetized animals and cat encéphale isolé preparations.2. On the isolated guinea-pig ileum an initial dose of CS produced a small, non-maintained contraction. Subsequent doses had reduced effects. There was no effect on peristalsis when the substance was given intraluminally.3. No significant effects of CS were detected on the rat phrenic nerve-diaphragm preparation, the isolated perfused rabbit heart or on the contractor response of the indirectly stimulated cat tibialis muscle.4. In the cat encéphale isolé preparation 1 mg/kg (i.v.) produced a brief period of electrocortical alerting but no abnormal activity in the electrocorticogram. Doses in excess of 10 mg/kg produced cortical depression.5. Intravascular injection into the chloralose anaesthetized cat resulted typically in a pressor response accompanied by a brief period of apnoea. The threshold dose for the pressor response varied with the route of administration, but generally lay between 2.5 and 12.5 mug/kg; the threshold dose for apnoea was slightly higher. Small variations in this pattern of response were seen with different species and other anaesthetics.6. When administered by stomach tube to chloralose anaesthetized cats, CS produced no measurable effects at doses of up to 100 mg/kg.7. No changes in blood pressure or respiration were detected in anaesthetized cats given pure CS aerosol for 1 h in concentrations of between 345 mg/m(3) and 1.39 g/m(3) via a tracheal cannula or through the upper respiratory tract. Pure CS solution given by slow intravenous infusion at a similar dose and over a similar period produced significant effects on blood pressure and respiration.8. Pyrotechnically generated (grenade) CS produced variable effects when given by inhalation in concentrations of between 460 and 1,040 mg/m(3) for 1 hour. Respiratory depression, possibly reflex in nature, regularly occurred when the material was given via the upper respiratory tract, and respiratory stimulation occurred when it was given via a tracheal cannula.9. Some cats were pre-exposed to a dose of 500 (mg/min)/m(3) on 4 successive days and on the fifth day anaesthetized and exposed to high concentrations of grenade CS. Three out of six cats died during or after this final exposure compared to one out of six among animals not so pre-exposed. The general pattern of response to the final exposure to CS in the two groups was similar.