^{page 449 note *} Christison, , “A Treatise on Poisons,” 1845, p. 836Google Scholar; Trousseau, and Pidoux, , “Traité de Thérapeutique et de Matière Médicale,” tome ii. 1862, p, 55Google Scholar; Pereira, , “The Elements of Materia Medica and Therapeutics,” vol. ii. part i. 1855, p. 549Google Scholar; Stillé, , “Therapeutics and Materia Medica,” vol. i. 1868, p. 770Google Scholar; Gubler, , “Commentaires Thérapeutiques du Codex Médicamentarius,” 1868, p. 602Google Scholar; Th., and Husemann, A., “Handbuch der Toxikologie,” Erste Hälfte, 1862, p. 465Google Scholar; Tardieu, , “Étude Médico-Légale et Clinique sur l'Empoisonnement,” 1867, p. 750Google Scholar; Taylor, , “The Principles and Practice of Medical Jurisprudence,” 1865, p. 358Google Scholar; Schroff, , “Lehrbuch der Pharmacologie,” 1868, p. 508.Google Scholar

^{page 449 note †} Since this was written, I have communicated with Dr John Harley, of London (the author of several important papers on the physiological action and therapeutical employment of belladonna), and have had the satisfaction of learning that he. also has observed tetanus, and other symptoms of abnormal reflex activity, in frogs during protracted atropia-poisoning.

2d March 1869.—I quote the following reference to these symptoms from a work which Dr Harley has published since this paper was communicated:—“The action of atropia leaves the frog in an excessively nervous state; the least disturbance causes great agitation, with increase of the respiratory movements, and a touch often throws the animal into a tetanic convulsion.”—The Old Vegetable Neurotics, 1869, p. 240.Google Scholar

^{page 451 note *} The numbers of the experiments of which detailed descriptions are given in this section have reference to the arrangement in Table I. at the end of the section.

^{page 451 note †} This instrument was employed in all the experiments in this investigation.

^{page 459 note *} Although this is “usually” the case, continuous tonic spasm of the anterior extremities may be produced by strychnia also, if an extremely small dose be given. I have found that a dose equivalent to about the th of the weight of a male frog (or of a female in whom the abdomen is not greatly enlarged by distended oviducts) will almost invariably cause continuous spasm and arch-like flexion of the anterior extremities; and Tardieu (op. cit. p. 983) describes the same effect in an experiment with a minute dose of strychnia.

^{page 468 note *} Archives de Physiologie Normale et Pathologique, 1868, p. 472.Google Scholar

^{page 468 note †} Transactions of the Royal Society of Edinburgh, vol. xxiv. part iii. p. 743.Google Scholar

^{page 468 note ‡} Leçons sur la Physiologie Générale et Comparée du Système Nerveux. Paris, 1866, p. 457Google Scholar.

^{page 471 note *} The experiments in this series were all performed in winter, when the low temperature of the laboratory was favourable to a long-continued retention of nerve-irritability in parts cut off from the circulation.

^{page 475 note *} De la Méthode Physiologique en Thérapeutique et de ses applications a l'étude de la Belladone. Paris, 1868, p. 51Google Scholar, &c.

^{page 475 note †} Meuriot, op. cit. p. 98.

^{page 475 note ‡} Lectures on the Diagnosis and Treatment of the Principal Forms of Paralysis of the Lower Extremities. Philadelphia, 1861, pp. 51 and 112.Google Scholar

^{page 475 note §} Rosenberger, quoted by Tardieu, op. cit. p 752; Schroff, , Lehrbuch der Pharmacologie. Wien, 1868, p. 508.Google Scholar

^{page 476 note *} Martin-Magron, MM. et Buisson, , “Action Comparée de l'Extrait de Noix Vomique et du Carare,” Journal de la Physiologie de l'Homme et des Animaux, 1859, p. 487Google Scholar; DrSpence, A. J., “On the Mode of Action of Strychnia,” Edinburgh Medical Journal, July 1866, p. 50.Google Scholar

^{page 477 note *} Meuriot, loc. cit. p. 98, &c. Brown-Séquard, , “Lectures on the Diagnosis and Treatment of Functional Nervous Affections,” 1868, p. 66.Google Scholar Both authors account for the increased excitability of the spinal cord by dilatation of blood-vessels—a method of causation which, I believe, cannot be established by any evidence that we at present possess.

^{page 478 note *} “Recherches Expérimental et Cliniques sur les Alcaloïdes de la famille des Solanées.” Archives Générates de Médicine, 1865, vol. ii. p. 175Google Scholar.

^{page 478 note †} Op. cit. p. 177. I have in my possession notes of many experiments supporting this proposition, but have preferred to quote evidence obtained from an investigation in which this marked difference between the effects of different doses is not specially alluded to.

^{page 478 note ‡} That this difficulty in causing complete paralysis does not occur with frogs, is due to their endowment with the function of cutaneous respiration. In this animal, reflex activity may be so far impaired by the action of a poison, that pulmonary respiration is rendered impossible, and yet asphyxia may not take place to such an extent as to bring the circulation to a stand-still, and the poison may thus be allowed sufficient time to produce on the living nerve-structures its complete physiological effects.

^{page 478 note §} Vulpian, op. cit. p. 196.

^{page 478 note ∥} This action has already been demonstrated by Botkin, Virchow's Archiv, Bd. 24, 1862, p. 84; by Bezold, Von and Bloebaum, , Untersuchungen aus dem Physiologischen Laboratorium in Würzburg, l^tes Heft, 1867, p. 13Google Scholar; and by Meuriot, op. cit. p. 90. The last author attempted to prove that it is the result of a local action on the nerves by imbibition, and not of poisoning through the blood; but his arguments seem insufficient to establish this view. I hope to refer more fully to this objection on some future opportunity.

^{page 480 note *} AB, line of normality, each division of which, ot ₁, t ₁t ₂, t ₂t ₃, &c., represents a period of twenty-four hours; CD, line of complete paralysis; op ₁p ₂p ₃, &c., curve of paralysis; os ₁s ₂s ₃, &c., curve of spinal-stimulant (tetanus, &c.); t ₁p ₁, t ₂p ₂, &c., ordinates whose length roughly represents the amount of the paralytic action; t ₁s ₁, t ₂s ₂, &c., ordinates whose length roughly represents the amount of spinal-stimulant action.

^{page 481 note *} AB, line of normality, each division of which, ot ₁, t ₁t ₂, t ₂t ₃, &c., represents a period of ten minutes; CD, line of complete paralysis; op ₁p ₂p ₃, &c., curve of paralysis; os ₁s ₂s ₃, &c., curve of spinal-stimulation (tetanus, &c.); t ₃p ₃, t ₄p ₄, &c., ordinates whose length roughly represents the amount of the paralytic action; t ₄s ₄, t ₅s ₅, &c., ordinates whose length roughly represents the amount of spinal-stimulant action.

^{page 483 note *} AB, line of normality, each division of which, ot ₄, t ₄t ₈, t ₈t ₁₂, &c., represents a period of forty minutes; CD, line of complete paralysis; op ₄p ₈p ₁₂, &c., curve of paralysis; os ₄s ₈s ₁₂, &c., curve of spinal-stimulation (tetanus, &c.)

^{page 484 note *} AB, line of normality, each division of which, ot ₁, t ₁t ₂, t ₂t ₃, &c., represents a period of ten minutes; CD, line of complete paralysis; op ₁p ₂p ₃, &c., curve of paralysis; os ₁s ₂s ₃, &c., curve of spinal-stimulation (tetanus, &c.); t ₁p ₁, t ₂p ₂, &c., ordinates whose length roughly represents the amount of the paralytic action; t ₂s ₂, t ₃s ₃, &c., ordinates whose length roughly represents the amount of the spinal-stimulant action.

^{page 484 note †} It is probable that a stage of tetanus occurring subsequently to a stage of paralysis has never been observed in mammals, after the administration of atropia, because a sufficiently large dose cannot be administered without causing death while the paralytic effects are being developed. It is, however, possible that separate paralytic and tetanic stages might be produced in mammals, if artificial respiration were employed after the administration of a very large dose.

^{page 484 note ‡} AB, line of normality, each division of which, ot ₄, t ₄t ₈, t ₈t ₁₂, &c., represents a period of four hours; CD, line of complete paralysis; op ₄p ₈p ₁₂, &c., curve of paralysis; s ₄s ₈s ₁₂, &c., curve of spinal-stimulation (tetanus, &c.); t ₄p ₄, t ₈p ₈, &c., ordinates whose length roughly represents the amount of the paralytic action; t ₄t ₄, t ₈s ₈, &c., ordinates whose length roughly represents the amount of the spinal-stimulant action.

^{page 485 note *} This action of sulphate of methyl-strychnium has been demonstrated by Dr A. Crum Brown and the author in a paper read before this Society, and published in the Transactions, vol. xxv. part i. pp. 151–203. I prefer this substance to curara, because of its strength being constant; and on this ground I would recommend it to physiologists and physicians.

^{page 487 note *} AB, line of normality, each division of which, ot ₁, t ₁t ₂, t ₂t ₃, &c., represents a period of twenty-four hours; CD, line of complete paralysis; op ₁p ₂p ₃, &c., curve of paralysis; os ₁s ₂s ₃, &c., curve of spinal-stimulation; t ₁p ₁, t ₂p ₂, &c., ordinates whose length roughly represents the amount of the paralytic action; t ₁s ₁, t ₂s ₂, &c., ordinates whose length roughly represents the amount of the spinalstimulant action.

^{page 488 note *} Loc. cit. pp. 160 and 196.