Pharmacological evidence for multiple sites of action of pressure in mice

The ability of eight diverse pharmacological agents to ameliorate the high pressure nervous syndrome (HPNS) in mice was studied. Data were obtained for the end points: coarse tremors, complete spasms, clonic convulsions, tonic convulsions, and death. The three anesthetics examined (nitrogen, urethane, and phenobarbital) gave good protection against all end points but especially against tonic convulsions. Furthermore, marked increases (greater than 90 atm) were recorded in the lethal pressure in spite of a fixed linear compression. Some detailed differences among the anesthetics were also noted. Of the anticonvulsants, phenytoin protected against tonic convulsions but actually exacerbated some other end points. Diazepam gave some protection against all phases except the tremors, as did trimethadione. Tetrahydrocannabinol and chlorpromazine had little effect. The pharmacological profiles of these end points are all different, suggesting they represent the effects of pressure at separate and distinct sites in the central nervous system. The HPNS cannot be regarded as a single syndrome.