TY - JOUR T1 - THE PHARMACOLOGY OF CENTRAL AND PERIPHERAL INHIBITION JF - Pharmacological Reviews JO - Pharmacol Rev SP - 333 LP - 364 VL - 15 IS - 2 AU - DAVID R. CURTIS Y1 - 1963/06/01 UR - http://pharmrev.aspetjournals.org/content/15/2/333.abstract N2 - The principal aim of pharmacological studies upon chemical inhibitory processes is the elucidation of the nature of transmitter agents. Before a given compound can be fully identified as the inhibitory transmitter operating at a particular synaptic region, it must satisfy all of the following requirements (73, 293): the conductance change induced in the inhibitory subsynaptic membrane must be identical with that of the natural transmitter; the substance must be present or synthesized in the appropriate synaptic terminals and released by stimulation of the inhibitory nerve fibres; the interactions of the compound with blocking and potentiating agents must be identical with those of the transmitter. When examined in the light of these requirements very few substances qualify as proven transmitters. In particular, it is difficult to satisfy the criterion that the substance be located in and released from inhibitory nerve terminals, and it is usually sufficient to demonstrate that the substance can be extracted from the tissue and is released by inhibitory nerve stimulation. Future investigations of this nature will be aided by several comparatively recent techniques. These include the histochemical localization within tissues of particular compounds; the technique of separating subcellular particles, especially nerve endings (94, 375); and the ability to determine quantitatively enzymes of single neurones (169) which may be associated with the manufacture and inactivation of transmitters. At the present time it is generally accepted that acetylcholine is the cardiac vagal inhibitory transmitter in mammals and amphibia. However, no other vertebrate inhibitory transmitter has been identified, and none of the substances which have been proposed as transmitters satisfies the requirements discussed above. The only positive finding with respect to postsynaptic inhibition in mammals and amphibia is the specific blocking action of tetanus toxin, strychnine, and closely related compounds. Presynaptic inhibition in the mammalian spinal cord, which is resistant to strychnine, appears to be diminished by picrotoxin, which does not diminish postsynaptic inhibition. It is unknown to what extent this action of picrotoxin explains its stimulant effect upon the central nervous system. Studies upon invertebrate inhibition indicate the strong possibility that acetylcholine is an inhibitory transmitter in Aplysia depilans, but the transmitters for the inhibition of crustacean stretch receptors and at the crustacean neuromuscular junction remain unknown. At both of these latter sites the blocking action of picrotoxin appears to be specific. ER -