Interactions of Central Depressants with Amino Acids and Their Antagonists

Abstract

Since their introduction over 70 years ago, barbiturates have been invaluable therapeutic and experimental agents. While they possess a wide spectrum of pharmacological actions e.g. hypnotic, anaesthetic, anticonvulsant, their precise mechanism and site/s of action remains obscure. A multitude of actions on synaptic processes have however been proposed. Thus in vitro and in vivo studies suggest actions on cell metabolism (see Sharpless 1970) neurotransmitter synthesis (Richter & Crossland, 1949; Anderson & Bonnycastle, 1960; Corrodi et al, 1966) release (Mitchell, 1963; Phillis & Chong, 1965; Phillis 1968; Cutler & Dudzinski, 1974) and inactivation (Cutler et al, 1974). More specifically they have been suggested to affect a number of post-synaptic processes, for example, they modify the actions of putative excitatory neurotransmitters acetylcholine and glutamate (see Bradley & Dray, 1 973). Perhaps of greater significance, barbiturates have been shown to increase the duration of central pre-and post-synaptic inhibition at spinal and supra-spinal sites (Eccles et al, 1963; 1971; Nicoll et al, 1975), processes considered to be mediated by GABA. Although a direct action on post-synaptic GABA receptors may account for these effects (Nicoll, 1975) other interactions with post-synaptic events triggered by GABA e.g. ionic conductance changes, may also be involved (Ransom & Barker, 1976).