Introduction

Although curare and gallamine are usually known for their neuromuscular blocking actions, it has always been appreciated that they may also have significant effects on the central nervous system (CNS). As early as 1812 (Brodie, cited in Smith et al., 1947) it was believed that curare acted on the brain. There are many other references to a central action of curare in the nineteenth century. Since the initial laboratory investigations into gallamine a central action has been recognized (Salama & Wright, 1952a).

Curare

The early history of curare is interesting but not particularly informative about its central action for two reasons. Firstly, prior to the early 1940s curare extracts were a mixture of substances, of variable and uncertain composition. The introduction of the pure alkaloid, d-tubocurarine, meant that henceforth it was possible for the results from different laboratories to be legitimately compared. Secondly, in many experiments the drug was injected intravenously. d-Tubocurarine (dTC) crosses the blood–brain barrier sparingly. Under certain conditions, e.g. in certain pathological states, the blood–brain barrier may be breached and more drug may pass over. As a result, there has been much confusion and disagreement in the studies in which dTC was administered parenterally. For a proper analysis the drug must be injected into the CNS or into a brain cavity. Earlier references are summarized in McIntyre (1947) and Smith and colleagues (1947).

Injection of dTC into the subarachnoid space produced a wide range of effects. Salama & Wright (1950) injected dTC intraventricularly and intracisternally in chloralose-anaesthetized or decerebrated cats and caused excitation of the vasomotor, respiratory and cardiac systems and also elicited autonomic effects, especially on the salivary glands and bronchi.