An alkaloid obtained from Hyoscyamus, C17H23NO3.
1 a. The active principle of Hyoscyamus, when given in small doses, such as are insufficient to produce positive dryness of mouth, rapidly subdues ordinary excitement of pulse, and reduces it within an hour or two to its lowest rate, that is to say, to the condition in which it is usually found after a long period of complete rest of mind and body. For example, the pulse of a man ordinarily engaged shall be 80. After gr. 1/40 of sulphate of hours it will gradually fall to 60 or 50. In another person, whose pulse may be 72, we shall at the end of the same time find it steadily beating about 45. In all my experiments I have never observed the pulse to fall lower than 40.
1 b. After doses (gr. 1/16 to 1/12) sufficient to produce complete dryness of tongue, and of hard and soft palates, the pulse will generally experience an acceleration of 10 or 20 beats, and be increased in force and volume. This acceleration will generally be observed 10-20 m. after the subcutaneous injection; it does not usually continue longer than 20-30 m., and rarely lasts an hour. Then the pulse slowly declines, and gains a little in fore and volume. It usually decline by about 5 beats for every interval of 20 or 30 m. until, after 1 1/2 or 2 hours, it attains its minimum rate. Apart from these effects on the pulse, the following symptoms will be observed after moderate dose (gr. 1/30 to 1/24):- In 10-20 m. tongue more or less completely dry, rough, and brown, hard and soft palates dry and glazed excessive giddiness, and a weight across forehead, somnolence, cheeks occasionally a little flushed, and membranes of eye sometimes slightly injected. After continuing about an hour these symptoms pass off; and tongue, with hard and soft palates, becomes covered over with a sticky and offensive secretion, agreeing in all respects with that which follows the action of belladonna. The pupils slowly dilate during the latter part of the action of the medicine, and at its close attain their maximum degree of dilation.
1 c. If larger doses than gr. 1/12 be given the above- mentioned effects will be increased and prolonged for 2 or 3 hours; and they will be accompanied either by wakeful, quiet, and usually pleasing delirium with illusions of sight; or with such excessive somnolency that patient cannot keep eyelids raised for a few seconds, but when aroused lapses again into a dreamy sleep, broken by occasional mutterings and slight jerking of limbs. In either case the power of maintaining and slight jerking of limbs. In either case the power of maintaining the erect posture will be lost, and at best patient reels like a drunken man. (HARLEY, op. cit., p. 322.)
2. a. Samuel M-, at. 49, in strong health save of facial neuralgia. Pulse 74; pupils 1/9″; resp. 20. Had gr. 1/24 subcutaneously injected. After 23 m. pulse 89. After 3/4 hour, pulse 84, regular; giddiness; tongue dry and hard. After 1 hour, pulse normal; mouth clammy, throat dry. After 2 hours, pulse 72; pupils 1/8″; mouth quite moist; throat felt very dry.
2 b. Gr. 1/10, given in same way. After 20 morning, pulse 92, regular; great somnolency; excessive giddiness; he staggered much in walking. After 1 hour, pulse 82; pupils 1/8″; legs felt too weak, and he was too giddy, to walk without assistance; continued very sleepy; no dryness of mouth. After 1 1/2 hours, pulse 79; pupils 1/7″; still giddiness and somnolency; mouth and throat very dry and parched since last date, and remained so. After 2 hours, pulse 72, otherwise normal; pupils 1/6″; tongue dry and brown in centre; both palates dry and glazed; somnolence nearly gone, but giddiness continued, and he still required help in walking. After 2 1/2 hours, giddiness and dryness passing off. (Ibid.)
3. a. Charles V-, aet.32, strong man with chronic lumbago. Pulse 76; pupils at light 1/10″, sideways 1/7″. 1/48 gr. injected. After 20 morning, pulse 58. After 3/4 hour, pulse 55; pupils 1/8″, sideways 1/6.” After 1 hour, pulse 54; after 1 3/4 hour, 51; inclined to yawn. After 2 1/4 hours pulse 50; pupils as at 3/4 hour; slight dryness of month. At first force and volume of pulse were slightly increased, but afterwards it continued unchanged and regular throat. There was neither somnolency nor giddiness.
3 b. 1/20 gr. After 40 morning, pulse 66. Giddiness came on 10 morning after injection, and he now staggered a little on rising from chair; no somnolency; pupils slightly dilated; mouth generally dry. After 2 1/4 hour, pulse 52, otherwise normal; pupils 1/7″, sideways 1/5″.
3 c. 1/12 gr. After 20 morning, pulse 91, a little increased in volume; face a little flushed; felt heavy. After 1 hour, pulse 80; pupils 1/8″, sideways 1/7”; sclerotics and conjunctivae a little injected; face-chiefly cheeks -hot and flushed; tongue dry and brown down centre, rest of mouth very clammy; much somnolency and giddiness; he had slept last 10 m. After 2 hours, pulse 56; pupils 1/7″, sideways 1/5; flushing, etc., quite gone; mouth moist and clammy, and exhaling offensive odour; he had slept during last hour, and still experienced somnolency.
3 d. 1/8 gr. After 30 morning, pulse 102, of undiminished volume and power; pupils 1/8″; conjunctivae a little injected; tongue uniformly dry; both palates dry and glared; dull, heavy, and sleepy, and very giddy, reeled much in walking. Giddiness and dryness came on 12 morning after injection. After 40 morning, pulse 100; after 50 m. 88, eyes suffused, eyeballs restless, face hot and flushed; looked very heavy had slept, and great somnolency continued; mouth still moist. After 1 1/4 our pulse 67, otherwise normal; pupils 1/7″, sideways 1/5″; face less flushed; mouth quite moist, but throat very dry, and during last hour a dry tracheal cough was present; very giddy and sleepy still; frequently yawned and sighed. After 2.1/4 hour., pulse 58, softer; pupils 1/6″, sideways 1/4″ nearly; flushing, etc., had disappeared; somnolency now passing off. After 3 hours pulse 53; pupils as at 2.1/4; face and eyes natural; mouth moist; no other after – effects, and he now walked a distance of 4 miles.
e. The following table shows effect on urine:
Obs. Urine before med. Urine after med. a. 11.7 a.m. Between 8:30 and 11.7 3v, sp. gr. 1015, acid, pale sherry colour 2 1/4 hours after injection 3xviiss passed, sp. gr. 1010, feebly acid, whey coloured. 1/30 gr.at 8:30-11:15 3v, 1016 acid, much 11:15 a.m. uric acid 2 hours after 3xvss, 1008, alkaline, much less uric acid. b. 8:30 – 10:30 3xj, quality as above. 2.1/2 hours after 3xviij, 1008, 10.30 a.m. neutral, a trace of uric acid. 10:30 a. m. c. 8:30-11 3xiiss, 1010, faintly acid. 2 hours after 3xviiss, 1005, very alkaline. 11 a.m. d. 8:30-10.47 3viij, 015, acid, 10.47 a.m. bright on boiling. 1000 gr. measures contained 2.1/2 hours after 3xiv, 1008, alkaline, phosphatic opalescence on boiling. 1000 gr.contained: chlorine. g. 1:55 Chlorine gr.2:95 Urea gr. 12.32 Urea gr. 5.33 Sulphates and phosphates gr.4.16 Sulphates and phosphates gr. 3.24. (Ibid.) 4. Mrs.F-, aet.47; pulse 72; pupils at light 1/8″. 1/24 gr. caused great somnolency for 3 hours, with tottering and giddiness, so that she had to make two or three efforts before she could raise herself from the chair, and then began to reel and could not walk safely without support. Felt a great weight across forehead. Pulse during first 15 morning fell 16 beats, and during next 2 1/4 hours 8 beats more, when it attained the minimum, numbering 48. During the next hour it rose to 40 At end of 30 m. tongue was dry and brown, and both palates dry and glazed, remaining thus for following 1 1/2 hour 3 1/2 hours after injection, pupils measured 1/5″, and general symptoms had passed off completely. (Ibid.)
5. Mrs.E.W-, aet.34, storage and healthy, but suffering from neuralgia of fingers; in much pain, pulse 88 after sitting hour, pupils 1/10”. In 15 m. after injection of gr. 1/24 pulse decreased 6 beats; once or twice a. m. a beat came very slowly, otherwise quite regular;much somnolency and giddiness. After 30m. pulse further decreased 2 beats, quite regular, slightly increased in volume and power; tip of tongue and hard palate quite dry; face hot and flushed; still very sleepy. After 3/4 hours mouth suddenly and completely moistened, and at same minute pulse fell 7 beats, and attained minimum depression of 19 beats; flushing of face began to decrease; pupils 1/8″, sideways 1/6”,; somnolency and giddiness remain, and she continued to sleep during next 1 1/2 hour, when disturbed awaking with a start. At end of this time pulse was 72, having increased 3 beats since last mention; it was regular, and of slightly increased volume and force. (Ibid.)
6. John C-, aet. 55, an able-bodied but weakly man, had gr. 1/5 injected for relief of obstinate neuralgia. After 5 m. giddiness. After 20 m. pulse increased 12 beats, full and regular; tongue and mouth generally dry; hard palate quite dry; pupils dilating; felt sleepy and giddy. On attempting to rise from chair, he began to reel; legs were very weak, and he could not walks without assistance. After 45 m. pulse increased only 2 beats, of natural volume and force; pupils dilated to 1/5″; tongue, except margin, quite dry and rough; both palates completely dry and glazed; articulation indistinct from great dryness of tongue and throat. Complained of giddiness across forehead; no somnolency. Mind quite clear when engaged in conversation, but when left undisturbed he relapsed into a dreamy condition with eyes wide open. Twice he reached out a hand to an object on the table, and began to look about on the floor, and when I asked him “what for?” he said, “Oh! I thought something had dropped of the table- the walls appear to move a little. ” There was no flushing of the face or injection of the eyes. He could not rise from his chair, or walk without assistance; and as he sat, the extensors of the legs were slightly twitched now and then, so as to advance the foot with a little jerk. After 1 hour, pulse 1 beat less, full and regular; pupils a little over 1/5″; excepting gums, mouth quite dry. Continued in same condition, without manifesting least tendency to sleep. He remained quiet, but inclined to be meddlesome when his attention was not engaged in conversation, grasping at objects on the table, or in the waste-basket on the floor, and attempting to remove them before hand reached them, evidently misjudging distance. The muscular system generally was flaccid, he did not sit erect in the chair, and (besides jerking of feet already mentioned) once or twice the hand was suddenly pronated and supinated with a jerk. After 2 hours, pulse had decreased 6 beats, but still remained of good volume and force; pupils between 1/5″ and 1/4″; mouth dry as before; no flushing of face or injection of eye, no headache or somnolency. In answer to my questions, he said that he only felt giddy. The limbs were fidgety, and occasionally affected with slight twitching. Left alone, he relapsed into a state of forgetfulness and dreamy meddlesome delirium, picking at objects, and, having reached them after several unsuccessful efforts, fumbling them about until he dropped them, and then, in the attempt to pick them up, losing his balance, and, but for constant attention, falling over. When aroused, he rubbed his hands, gaped, and answered my questions readily. He was quite unable to walk. The eyelids were unsteady. A remark which I made at this time excited a risibility which he was unable to restrain, and every now and then the suppressed chuckle burt out into a hearty laugh. During next 1 1/4 hour he became somewhat restless, and if I left his side for a morning, he would attempt to get up, reel for a few paces, and then fall together like a drunken man upon the carpet. At the end of this time the giddiness diminished, and a slight inclination for sleep came on. after 3.1/4 hours he was garish and tired. He could now walk without assistance, but still reeled a little. Anterior part and margins of tongue were now quite wet with an acid secretion. Eyeballs were still unsteady. After 3 3/4 hours pulse was 60, and normal as at 2nd hour; pupils were nearly 1/4″ at light; mouth everywhere moist, and cerebral symptoms rapidly subsiding. At this time he ate a plateful of cold meat; and 1/2 hour after only slight giddiness and heaviness remaining, he walked home. (Ibid.)
7. When in an adult 1-3 milligrammes are subcutaneously injected, in a few morning pupils dilate, and in 20-25 morning iris has disappeared. At same time, patient complains of dryness of throat and gums, which shows itself by involuntary acts of swallowing and constant mumbling There is much thirst and some dysphagia. There is a slight acceleration of pulse and breathing; also a little rise of temperature, but this is not constant. Dulness of head is complied of, and a slight excitement with tendency to movement; but the legs tremble, bend, and refuse their aid, as in intoxication. After an hour or two comes desire to sleep, lassitude; sometimes a slight delirium and a profound slumber succeed to this period of excitement. Next day nothing remains but sense of dryness of throat, and sometimes pupils still dilated. In impressionable persons there is occasionally disturbed vision, as diplopia; and in some unwonted erotic dreams, with or without pollutions. (LAURENT, de l’ Hyoscyamine et de laDaturine, Paris, 1870.)
8. a. To an adult, at 11:50 a. m., 3 hours after a meal, 2 gr. of amorphous alkaloid were given. Previous to administration pulse was 104, temperature 8.6o, respiration 20, pupils 1/8” At 12, pulse 94, respiration 18; otherwise same. 12:10, 12:10 pulse 80, respiration 18 mouth dry, giddiness. 12:20, pulse 116, respiration 20, temperature 98.7o, pupils 1/4, motion impaired. 12:30, same; drowsiness. 12:40, pulse 120, respiration 24, temperature 98.5o; motion more impaired. 12:50, temperature 98.9o articulation slow. 1.0, pulse 114, respiration 22, temperature 98.7o, mouth and nose very dry. 1:10, pulse 108, respiration 24, temperature 98.5o; interrupted sleep. 1:20, pulse 105, respiration 22, temperature 98.2o illusions and paralysis of accommodation. 1:30, pulse 100, respiration 21. 1:40, pulse 105, respiration 22; active dreams and involuntary exclamations. 1:50, pulse 106, respiration 20, temperature 9.6o; icterus.[*”The subject of the experiment was the only person who witnessed the existence of jaundice. It has never been seen in the course of numerous subsequent experiments.”*]. 2.0, pulse 100, respiration 21, temperature 98.2o; movement still impaired. 2:10, pulse 94, respiration 18, pupils (all this time at 1/4) 3/8”; incoherence and aphasia. From this time pulse, etc., were no longer recorded; mental state was characterized by heaviness, incoherence in conversation, and a certain amount of toxic aphasia, as shown by a tendency to slur over words and syllables. During following night sleep was disturbed by dreams, in which person affected frequently made short audible remarks, evidently in answer to subjective interrogations.
8 b. After 3 days, 3 gr. were given to same individual at 3:50 p. m. Pulse was 104, respiration 20, temperature 99 o, pupils 3/16. 3, pulse 108, respiration 19; lips dry, giddy. 4:15, pulse 112, respiration 22; great loss of motor power. 4:30, pulse 108, respiration 19, pupils 1/4; marked drowsiness. 4:40, pulse 116, respiration 23; voice husky, interrupted sleep. 5:10, pulse 126, respiration 22; could not walk alone. 5.23, pulse 110; interrupted sleep. 5:30, pulse 114; restless and incoherent. For 7 hours subsequently it was possible to take only occasional and irregular observations. During a long-continued display of delirious excitement pulse fluctuated irregularly between 104 and 1290, respirations fell to 14, and temperature reached a minimum of 98.4o and a maximum of 99.2o. During this stage of the action of the medicine the patient manifested all the symptoms of simple mania. He mistook identities, spoke incoherently, acted irrationally, and was frequently under the influence of delusions and hallucinations. Early in this period there was marked paralysis of ocular accommodation. Chairs, which were 5 or 6 feet distant were grasped as if within reach, and repeated efforts were required to rectify the mistakes originating in this aberration of vision. The full cerebral effect of the drug was manifested 2 hours after administration. he first symptoms was inability to fix the attention on any given subject. The patient, though rising from his seat for a definite purpose, immediately forgot what his own intentions were. He talked in incoherent snatches, and after commencing to express an idea passed suddenly on to the statement of another and apparently unconnected one, which also he left obscure and unexplained. While under the combined influence of delusions, hallucinations of sight, and paralysis of accommodation, he attempted to step from a window about 30 ft. from the ground stating that he was going out upon the lawn, which he was convinced was on a level with the window. He had numerous hallucinations of sight. A picture which, under the influence of a delusion, he had taken from the wall and placed on a sofa, he immediately afterwards sat upon in the belief that it was an embroidered cushion. He pointed to cats which he said, were standing on their hind legs and making fantastic movements, when no such animals were visible to others. Friends at a distance were spoken to as if sitting in parts of the room which were quite unoccupied. Female heads and faces were pointed at in the air as examples of perfect grace and beauty. The mistakes in identity were so complete that interrupted conversation was carried on with persons who had temporarily assumed the identity accorded to them by the patient. During the persistence of these personal delusions, statements, which were either unreservedly sincere or ludicrously inappropriate, were freely cited by suggestion. The patient several times partially changed his clothes with the intention of going out for special purposes – to work, to walk, or to dine; but every new suggestion led to a modification of dress, till, actuated in a totally different manner, he left his toilet incomplete, and directed his attention to new and equally absurd pursuits. Latterly the motor impairment became less marked, but the cerebral condition was characterized by greater incoherence in speech and extravagance in action. The patient tried repeatedly to wind up a gold watch with a corkscrew. Ideas were imperfectly expressed which at best had neither sequence nor relative connection. The patient walked in an aimless manner from room to room, but to a great extent avoided obstacles in his way. The emotional condition was one of quiet satisfaction and comparative good humour. When the influence of delusions required the use of personal restraint the patient met it more by illogical argument and exposition than by force. The cerebral condition during the time followed upon the short period of drowsiness was characterised by wakeful restlessness, till, 9 hours after the administration of the medicine, the patient, in a comparatively lucid interval, undressed and went to bed. Throughout the night he experienced numerous hallucination of sight. Lizards and other animals crawled on the bedclothes. A face-always the same-formed itself by the hollows and elevations of the cornice, but this delusion could be dispelled by mental analysis. Two sides of the room appeared to form the two pages of a book separated by the intervening angle and by the influence of hypermetropia seemed to rest upon the bed and lie open before the patient; but after fixed attention the vision appeared to recede till the elements of the delusion wee fully determined by their relation to surrounding objects. after a short period of interrupted morning sleep no traces of the operation of the drug remained, except wide dilatation of the pupils, some dryness of the throat, and slight lassitude. During the action of the drug there was no reddening of the skin or other appearance of eruption.[*”Since the time that this paragraph was written, I have had frequent occasion to see and demonstrate a decided rash produced by the use of H. It appears most frequently on the face and forearms, and is not unlike the eruption of measles.”*]. Though during the greater part of the time consciousness was not affected, scarcely a single incident anterior to the time of going to bed was remembered by the patient, neither could the events recorded recalled to his memory by any attempt to associate the vagaries which he had forgotten with those of which he head a dim recollection. While the physiological action of the drug lasted there was free diuresis but no vomiting or nausea. (LAWSON, W. Riding Asylum Medical Reports, vol. v.).
Experiments on animals
I. The action of hours on the lower animals is essentially the same as on man.[*So also state M.M.Oulmont and Laurent.–EDS.*]. (HARLEY, op. cit.)
2. M. M. OULMONT and LAURENT have arrived from their experiments on animals, at the following conclusions:
2 a. Hyoscyamine and daturine act especially on the sympathetic nervous system.
2 b. In small doses they reduce the capillary circulation; in large doses they produce paralysis of the vessels.
2 c. Arterial tension is increased by weak, diminished by powerful doses. These effects are not modified by section of the vagi.
2 d. Frequency of pulse is increased and fulness diminished.
2 e. Hyoscyamine renders movements of heart regular; daturine often produces intermittence and arrest of action. When applied directly, both alkaloids slow, and ultimately arrest, the beats.