Curare

CURARE, arrow poison, is extracted by South American Indians from the bark and roots of certain species of Strychnos, Strychnos toxifera Schomb., Strychnos castelnaeana, Strychnos cogens Benth., and several other plants. The extract obtained from these plants is concentrated and then dried in clay vessels over fire. The most common preparations of C. are Tibo-curare (in special bamboo tubes), Calebassencurare (in gourd flasks), and Topfcurare (in small clay pots). The different activity of these preparations is explained by the different method of preparation and, above all, by the admixture of various toxic substances. The most active preparation is Curare Macutchif. The Tibo-curare now on the market acts more weakly and is in general little suitable for physiological experiments because of its side action on the vessels and on the heart. Dry C. is preserved for a very long time, but in general it is better to use the fresh extract of the aforementioned plants. From C. it has been possible to isolate the active substance, the alkaloid curarine, the lethal dose of which is 0.00025 g per 1 kg of body weight. The action of C. has been studied by a whole series of researchers (Vulpian, Kuhne, Cl. Bernard, Kolliker, Tarhanov, etc.). Among the symptoms of poisoning, paralysis of striated muscle takes first place, which in warm-blooded animals is the direct cause of death due to the cessation of respiration. To this specific action of C. is added the toxic action of various admixtures. Experiments by Claude Bernard and others have established that paralysis of striated muscle is the result of the action of C. on the motor plates of the motor nerves, i.e., on the synapse between the muscle and the nerve. Claude Bernard and Kelliker's classic experiment is as follows: the sciatic nerve is exposed on both legs of a frog, on one of the legs the vessels are ligated, the nerve having been previously isolated with care, and 1 cm³ of a 1:10,000 solution of C. is introduced into the lymph sac. After a few minutes, a decrease in mobility is noted, breathing ceases, and gradually a paralysis of the whole body appears, except for the leg on which the vessels are ligated: it retains voluntary movements and responds reflexively to irritation in any part of the body. Direct irritation of the muscles in the paralyzed part of the body causes their contraction. From this experiment, Cl. Bernard concluded that C. acts neither on the nerve centers nor on the nerve trunk nor on the muscle itself, but acts exclusively on the elements connecting the muscle with the nerve. This conclusion was confirmed by Kuhne, who showed that the motor plates of striated muscle change under the influence of C.: they become less transparent and more granular than in the normal state. The action of C. manifests itself more quickly on fatigued muscles, as well as after cutting the corresponding motor nerve. - According to observations on man and on animals, C. in weak doses exerts a very weak inhibitory action on the brain and on the medulla oblongata; in strong doses it acts on the entire central nervous system, judging by the gradual disappearance of reflexes and voluntary movements in the unpoisoned leg. In strong doses, C. lowers the blood pressure by paralyzing the vasomotor centers, and finally paralyzes the heart as well. These phenomena are probably caused not by the specific substance of C. itself, but by the admixtures contained in it. The insensitivity of the nerve centers to the action of C. is explained by Stern and Gautier (Gautier) by the resistance of the hemato-encephalic barrier to the passage of C. from the blood into the cerebrospinal fluid and into the nerve centers. When C. is introduced into the cerebrospinal fluid (ventricles) or into nerve tissue, strong irritation of the nerve centers is noted, expressed in the strongest excitement, convulsions, increase in t°, etc., and leading to the death of the animal. - C. acts differently on different species of animals. In general, C. exerts a lethal action only on warm-blooded animals due to paralysis of respiratory movements. In animals possessing cutaneous respiration, C. causes only a temporary paralysis of striated muscle, and as C. is eliminated from the organism, the animal recovers. Jellyfish are not sensitive to C.; fish, like crabs, are little sensitive. - In experimental physiology, C. has found wide application in all those cases where it is required to exclude striated muscle without destroying the nervous system. However, such application of C. can be a source of experimental errors due to the difficulty of taking into account the side action of C. (on the autonomic nervous system). Thus, Holtz's experiment is not successful even in weakly curarized frogs. - In therapy, C. was used with some success in various forms of tetanus. The therapeutic dose can reach 0.03–0.05 g (according to Hager, the maximum dose is 0.02 g and pro die 0.06). When applying C., it is necessary to anticipate the possible need for artificial respiration. C. acts significantly more weakly when administered enterally, which is explained partly by the change in its digestive juices and partly by the neutralization by the liver.