- Email: [email protected]
Who makes it?
March, 1955
SCIENTIFIC EDITION
able to utilize two different placebo forms identical in appearance to the commercially available products: a pulvule form (Elorhe@ Sulfate, Eli Lilly and Co.) and a sugar-coated compressed tablet (Tricoloid@,Burroughs Wellcome and Co.). Thus the interchange of pulvule and tablet or pulvule placebo and tablet placebo tended to reduce the weight of the psychological factor inherent in all placebo-controlledstudies. The depression of locomotor activity in rats by low doses of tricyclamol may conceivably account for the drowsiness reported by some subjects undergoing anticholinergic therapy. In our opinion, the degree of depression exhibited is not sufficient to warrant discontinuing the practice of combining these agents with a sedative component, particularly in peptic ulcer therapy. Since acetylcholine is the chemical mediator of nerve impulses to skeletal muscles, it is logical to assume that large doses of tricyclamol effectively block the effect of acetylcholine at these sites and prevent locomotion in the rat. In our experience, only toxic doses will produce central stimulation in rats. SUMMARY 1. One hundred and seventy-three quantitative determinations of sweat on seven different areas of the body were performed before and after tricyclamol administration. Suppression of sweating was greatest on the forehead and dorsum of the hand and least on the upper arm and thigh. 2. Under the experimental conditions stated, it appears that tricyclamol reaches a point of effectiveness somewhere between thirty and sixty minutes and a peak of effectiveness between sixty and ninety minutes. The duration of action was four and one-half to five hours. 3. Tricyclamol effectively controlled hyperhidrosis in 76 per cent of a group of 75 hidrose subjects administered the compound in varying doses for six weeks to four months. Dosages up to 300 mg. daily were ineffective in controlling hyperhidrosis in 18 subjects.
163
4. Quantitative estimations of the parotid salivary output of 143 volunteer males were performed before and at half-hour intervals, after ingestion of 100 mg. tricyclamol. The maximum percentage of salivary suppression, which occurred a t the sixty minute post-drug period, was 26.8 per cent. 5. The anhydrotic and antisialogogue actions of tricyclamol compare favorably with those of other anticholinergics studied under similar experimental conditions. 6. Subjective manifestations of parasympathetic inhibition, substantiated by placebo administration and double blind studies, were reported by two controls and 21 hidrose subjects. A majority of the side effects were reported by subjects at a daily dosage schedule in excess of 200 mg. Only two subjects were forced to discontinue the medication due to persistent mydriasis. 7. Under the experimental conditions stated, low doses of tricyclamol inhibit locomotor activity in the rat. It would appear that only toxic doses produce central stimulation. 8. Tricyclamol fails to meet certain arbitrary requirements of an ideal anticholinergic agent. Nevertheless, continued progress is being made toward attainment of this objective.
REFERENCES (1) Zupko. A. G.. THISJOURNAL, 41, 212(1952). (2) Zupko, A. G . , and Prokop, L. D., ;bid., 41, 651
rl!XWi ,----,.
(3) Zupko, A. G., and Prokop, L. ‘D., ibid., 43, 35(1954). (4) Zupko, A. G . , and Prokop, L. D., ibid., 4.: 219(1954). (5) Beckman, H., “Drug Therapy 1953-54, Year Book Publishing Co.. Chicago, Ill., p. 493. (6) Shirley, M., J . Comp. Psycbal., 8, 23(1928). p7 (7) Skinner J. J . Gen. Psychol. 9.3(1933). (8) Fams, E. j.,and Griffith, J: Q., “The Rat in Laboratory Investigation,” 2nd ed., Lippincott Co., Philadelphia, Pa. 1949, p. 204. (9) Baird. J. A,, and Boyd, E. M., J . Pharm. and Pharmacol. 6,38 (1964). (10)’ Boyd, E. M., and Miller, J. K.. Federalion Prw., 13, 338(1954). (11) Shutkin. M . W., Am. J . Gastroenferology. 21, 386 (1954).
WHO MAKES IT? The Registry of Rare Chemicals, Armour Research Foundation of the Illinois Institute of Technology, 35 West 33rd Street, Chicago 16, Ill., seeks information on sources of supply of the following chemicals: Urushiol Veratridine Conessine Guanidine hydriodide Sphingosine Methoxyconiferine (Syringin) Traumatic acid Deoxyglucose Allocholesterol (Coprostenol) Bismuth ethyl camphorate
Cysteine sulfenic acid 5,7-Dihydroxyflavone (Chrysin) Aloetic acid Dulcitan L-Galactonic acid Ricinine Cellotriose Glutaconic dialdehyde Delta valerolactone Lecit hinase
~
SCIENTIFIC EDITION
able to utilize two different placebo forms identical in appearance to the commercially available products: a pulvule form (Elorhe@ Sulfate, Eli Lilly and Co.) and a sugar-coated compressed tablet (Tricoloid@,Burroughs Wellcome and Co.). Thus the interchange of pulvule and tablet or pulvule placebo and tablet placebo tended to reduce the weight of the psychological factor inherent in all placebo-controlledstudies. The depression of locomotor activity in rats by low doses of tricyclamol may conceivably account for the drowsiness reported by some subjects undergoing anticholinergic therapy. In our opinion, the degree of depression exhibited is not sufficient to warrant discontinuing the practice of combining these agents with a sedative component, particularly in peptic ulcer therapy. Since acetylcholine is the chemical mediator of nerve impulses to skeletal muscles, it is logical to assume that large doses of tricyclamol effectively block the effect of acetylcholine at these sites and prevent locomotion in the rat. In our experience, only toxic doses will produce central stimulation in rats. SUMMARY 1. One hundred and seventy-three quantitative determinations of sweat on seven different areas of the body were performed before and after tricyclamol administration. Suppression of sweating was greatest on the forehead and dorsum of the hand and least on the upper arm and thigh. 2. Under the experimental conditions stated, it appears that tricyclamol reaches a point of effectiveness somewhere between thirty and sixty minutes and a peak of effectiveness between sixty and ninety minutes. The duration of action was four and one-half to five hours. 3. Tricyclamol effectively controlled hyperhidrosis in 76 per cent of a group of 75 hidrose subjects administered the compound in varying doses for six weeks to four months. Dosages up to 300 mg. daily were ineffective in controlling hyperhidrosis in 18 subjects.
163
4. Quantitative estimations of the parotid salivary output of 143 volunteer males were performed before and at half-hour intervals, after ingestion of 100 mg. tricyclamol. The maximum percentage of salivary suppression, which occurred a t the sixty minute post-drug period, was 26.8 per cent. 5. The anhydrotic and antisialogogue actions of tricyclamol compare favorably with those of other anticholinergics studied under similar experimental conditions. 6. Subjective manifestations of parasympathetic inhibition, substantiated by placebo administration and double blind studies, were reported by two controls and 21 hidrose subjects. A majority of the side effects were reported by subjects at a daily dosage schedule in excess of 200 mg. Only two subjects were forced to discontinue the medication due to persistent mydriasis. 7. Under the experimental conditions stated, low doses of tricyclamol inhibit locomotor activity in the rat. It would appear that only toxic doses produce central stimulation. 8. Tricyclamol fails to meet certain arbitrary requirements of an ideal anticholinergic agent. Nevertheless, continued progress is being made toward attainment of this objective.
REFERENCES (1) Zupko. A. G.. THISJOURNAL, 41, 212(1952). (2) Zupko, A. G . , and Prokop, L. D., ;bid., 41, 651
rl!XWi ,----,.
(3) Zupko, A. G., and Prokop, L. ‘D., ibid., 43, 35(1954). (4) Zupko, A. G . , and Prokop, L. D., ibid., 4.: 219(1954). (5) Beckman, H., “Drug Therapy 1953-54, Year Book Publishing Co.. Chicago, Ill., p. 493. (6) Shirley, M., J . Comp. Psycbal., 8, 23(1928). p7 (7) Skinner J. J . Gen. Psychol. 9.3(1933). (8) Fams, E. j.,and Griffith, J: Q., “The Rat in Laboratory Investigation,” 2nd ed., Lippincott Co., Philadelphia, Pa. 1949, p. 204. (9) Baird. J. A,, and Boyd, E. M., J . Pharm. and Pharmacol. 6,38 (1964). (10)’ Boyd, E. M., and Miller, J. K.. Federalion Prw., 13, 338(1954). (11) Shutkin. M . W., Am. J . Gastroenferology. 21, 386 (1954).
WHO MAKES IT? The Registry of Rare Chemicals, Armour Research Foundation of the Illinois Institute of Technology, 35 West 33rd Street, Chicago 16, Ill., seeks information on sources of supply of the following chemicals: Urushiol Veratridine Conessine Guanidine hydriodide Sphingosine Methoxyconiferine (Syringin) Traumatic acid Deoxyglucose Allocholesterol (Coprostenol) Bismuth ethyl camphorate
Cysteine sulfenic acid 5,7-Dihydroxyflavone (Chrysin) Aloetic acid Dulcitan L-Galactonic acid Ricinine Cellotriose Glutaconic dialdehyde Delta valerolactone Lecit hinase
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