The interactions of anaesthetics and other drugs with high pressure suggest that protection against the
high pressure neurological syndrome (h.p.n.s.) can no longer be considered in terms of generalized non-specific mechanisms. The evidence from our work shows that anaesthetics may either protect, have no effect, or potentiate h.p.n.s. Structural analogues of the
steroid anaesthetic
Althesin have a protective effect against high pressure
tremors in spite of the fact that they have no anaesthetic effects. Low doses of
flurazepam are effective against
tremor but can be antagonized by
Ro 15-1788, which implies in this case a role for the
benzodiazepine receptor complex. Pressure interactions with other drugs have included the classic
anticonvulsants--which, in general, were relatively ineffective--and various agents perturbing the balance of specific
neurotransmitter systems. Representative examples from different studies include
6-hydroxydopamine,
muscimol, and
sodium valproate. Finally, the potent protection against h.p.n.s. by 2-amino-phosphonoheptanoic
acid, an antagonist with preferential action against excitation produced by
aspartate and
N-methyl-D-aspartate, provides the first evidence that enhanced
excitatory amino acid neurotransmission may have an important role in the h.p.n.s.