Muscarinum

Introduction

Muscarinum. – An alkaloid obtained from Agaricus muscarious, and also prepared artificially. Its formula is C5 H13 NO2H2O.

Provings

1. RINGER and MOREHEAD experimented on four men, giving gr. 1/3 or more to each hypodermically. Three of their patients were delicate and anaemic; the fourth had slight fever from some obscure cause, though his pulse was not quickened. Dr. Ringer presents their results as follows:

1a. Perspiration. – Sweating occurred in eleven out of the thirteen experiments. Half a grain always made it free, whilst large doses – as gr. 3/4 and 1 – rendered it very abundant, indeed, it was quite as free as the perspiration excited by gr. 1/3 – 1/2 of pilocarpine. Sweat stood in large drops on forehead after larger doses, nightdress became soaked and skin felt sodden. In one man only was perspiration absent, salivation taking its place. Sweating began in 3 – 15 m., occurring earliest after larger doses, and lasted for 1/2 – 1.1/2 h. Reaction of sweat in 6 cases was neutral in 4, alkaline in 2. 1b. Salivation occurred in 9 experiments, in 3 slight, in rest free or profuse; began in 2 – 15 m., lasted for 20 – 80 m.

1c. Lachrymation occurred in 8 cases, amounting in some merely to suffusion of eyes, but generally tears trickled down face, so that patient was obliged to wipe eyes. Began 6 – 10 m., lasted 20 – 30 m.

1d. Purgation. – In 2 instances drug excited inclination to stool; in 4 experiments on same man it produced a loose motion, one of a greenish colour, though bowels had been opened naturally a short time before. This effect followed in 10-20 m.

1e. Pulse in one of the four men was always very quick, in other three natural. In latter little change occurred, in one experiment only rate falling by 10 – 16 beats. Quick pulse was reduced from 120 to 80 or 60. Larger doses rendered pulse softer and more compressible. 1f. Respiration. – Unaffected in every experiment. 1g. Eyes. – Pupils always (15 m.) contracted, often considerably; vision unaffected. Applied to eyes muscarine causes wide dilatation of pupil, beginning in 15 – 45 m., and continuing about 24 h. Sight here also little affected.

In 3 experiments on one man larger doses induced vomiting once, nausea once. In 5 experiments patients were obliged to pass urine in 9 – 15 m. after injection, and 2 complained of supra- pubic pain. In 5 drug produced a frequent hacking cough. In no case did headache or other nervous symptoms occur. (Handbook of Therapeutics, 10th ed., p. 502.)2. SCHMIEDEBERG found 5 milligrammes produce in the human subject myosis, loss of focalising power, abundant secretion of saliva, determination of blood to head, flushed face, perspiration over whole body, giddiness, anxiety, griping and rumbling in bowels, and weight in head. (Von BOECK, in Ziemssen’s Cyclopaedia, xvii, 930.).

Experiments on animals

1a. The symptoms produced by muscarine in animals entirely correspond to those which poisonous fungi produce in the human subject. In cats we observe increased salivary secretion, vomiting, diarrhoea, rumbling in the bowels, staggering gait, contraction of pupils, frequency of respiration, dyspnoea. The vomiting and diarrhoea subside, respiration becomes less frequent, convulsions set in, respiration ceases, death supervenes.

1b. The intestine, under the influence of musc., becomes subject to tetanic contractions, so which the diarrhoea (or constipation), abdominal pains, &., are traceable. 1c. The influence of musc. on the heart and its contractions is very remarkable. When we inject gr. 1/130 subcutaneously into a frog, or bring a solution into director contact with the heart, this organ is almost immediately arrested in diastole. But if during this suspension of cardiac action, we irritate the heart in any way, it contracts – a proof that the cause of the cessation does not lie in the cardiac muscle. Section of the vagi has no effect upon this inaction of the heart caused by musc., therefore the inhibitory organs residing in the heart itself are strongly excited by the drug, and this excitement is powerful enough to counteract all the contractile power of the heart. (It is these same inhibitory organs which are paralysed by atropine.) This influence of musc. must produce an initial retardation of the heart stroke.

1d. In the early stage of the action of musc. respiration is more frequent and laboured than in the natural condition; later on there is a steady diminution of its frequency, till at last it ceases altogether. These symptoms of the respiratory apparatus proceed from an initial excitement and subsequent paralysis of the central organ in the medulla oblongata which govern respiration.

1e. The blood-vessels are constricted for a short time in the outset of musc. action, and afterwards dilated. The Vascular dilatation, combined with the diminished frequency of the cardiac pulsations, causes a decrease of blood pressure, amounting sometimes to one-third of the total amount.

1f. The flow of saliva which attends musc. poisoning is the consequence of an exciting influence exercised by musc. upon the peripheral extremities of the secretory nerves; at least we are led to this conclusion by the circumstance that section of these nerves does not affect the secretion of saliva.

1g. Krenchal has published (Arch. f. Ophthalm., xx, 1, 135) a very good report of the changes in vision produced by musc. Even small doses lead to disturbances in the accommodating power, which are characterised as “accommodation convulsions.” With somewhat larger doses a not very marked myosis sets in, dependent on excitement of the sphincter iridis itself, or on that of the oculo-motor nerve which governs it. The hypothesis of paralysis of the dilator pupillae or of the sympathetic nerve connected with it is inadmissible. (Ibid)

2. Schmiedeberg had noticed that intense dyspnoea was one of the most marked symptoms produced by musc. He had not, however, attempted to explain it. He had observed that during the dyspnoea the arteries contained very little blood, when cut across bled hardly at all. Desiring to ascertain the causation of this, Dr. Brunton thoroughly narcotised a rabbit with chloral, commenced artificial respiration, and opened the thorax. All was proceeding quite naturally until he introduced a little musc. into the jugular vein. “At once everything changed. The lungs became balanced, the left side of the heart small, the right side swelled up, and the vena cava became greatly distended.” A little atropine restored the normal state of things. (LAUDER BRUNTON, Brit. Medorrhinum Journ., 1874, ii, 617.)

3a. PREVOST found action of musc. on heart unmodified by destruction of nervous centres or by curare. there was no change be breathing in the frogs he experimented on, but in higher animals a violent dyspnoea was induced. He found even a feeble dose produce abundant salivation and lachrymation; former occurs quite as much after section of lingual or removal of superior cervical ganglion. Musc. excites the vermicular contractions of the intestines; he has seen hernia of the stomach drawn in under its influence. (Gaz. Medorrhinum de Paris, 1874, p. 243.)

3b. Same experimenter has subsequently found that the hepatic and pancreatic secretions are increased by it, but the renal diminished. (Comptes rendus de I’ Acad. de Medorrhinum, Aug. 10, 1876.)

4. RINGER and MOREHEAD find that if the intra-cardiac inhibitory centre (sinus venosus) is removed and musc. is then applied to the ventricle, it weakens and paralysis the heart, acting apparently on both the cardiac excito-motory apparatus and the muscular substance itself. (Journ. of Phys., 234, and Pract., xxvi, 4. In Journ. of Phys., iii, 59, Gaskell confirms direct action on muscular substance.).

Richard Hughes

Dr. Richard Hughes (1836-1902) was born in London, England. He received the title of M.R.C.S. (Eng.), in 1857 and L.R.C.P. (Edin.) in 1860. The title of M.D. was conferred upon him by the American College a few years later.

Hughes was a great writer and a scholar. He actively cooperated with Dr. T.F. Allen to compile his 'Encyclopedia' and rendered immeasurable aid to Dr. Dudgeon in translating Hahnemann's 'Materia Medica Pura' into English. In 1889 he was appointed an Editor of the 'British Homoeopathic Journal' and continued in that capacity until his demise. In 1876, Dr. Hughes was appointed as the Permanent Secretary of the Organization of the International Congress of Homoeopathy Physicians in Philadelphia. He also presided over the International Congress in London.