The Liberation of Histamine and Heparin by Tubocurarine and Its Circulatory Effects in the Dog
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Cited by 7 publications
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Meprobamate (Miltown, Fquanil) was synthesized in 1950 by Ludwig and Piech in an effort to find a muscle relaxant with longer duration of action and fewer sideeffects than mephenesin.1 In the initial pharmacological evaluation, Berger discov¬ ered three unusual attributes of meproba¬ mate which account in some part for its effectiveness as a tranquilizing agent, name¬ ly: (1) muscle relaxation due to selective blockage of interneuronal synapses bul without effect on monosynaptic reflexes, impulse transmission in peripheral nerves, or activity at the neuromuscular junction ;(2) peculiar "taming" effect on monkeys in that aggression disappears, and (3) thalamic stimulation.2 Although the drug has been in clinical use since 1954, reports of toxicity have been scattered, and only one review of adverse responses has appeared.3 One death has been reported.4 The purpose of this communication is to present a case of meprobamate idiosyncrasy with skin bi¬ opsy and skin testing, to review the pub¬ lished reports to date, and to discuss possible etiologic factors in the pathogene¬ sis of the anaphylactoid reaction.The records of more than 6500 patients have been summarized to date.8"81 Twentythree cases of attempted suicide,6"19 and one hundred thirteen cases of idiosyncrasy have been reported.18"68 Adverse responses to drugs may be con¬ veniently classified into five categories: (1) idiosyncrasy, (2) extension of a therapeu¬ tic effect, (3) allergic reaction, (4) poison¬ ous effect, and, (5) intolerance.82 In Idiosyncrasy.-Many new drugs astound patients and physicians alike by a dramatic but transient disturbance of homeostasis in the form of an anaphylactoid reaction fol¬ lowing ingestion of only one or a few tab¬ lets for the first time. Meprobamate is no exception, since about one patient in 200responds in this fashion, as in the following case report:A 39-year-old white man who had been taking promazine for six weeks without striking benefit because of insomnia, headache, jitteriness, and dyspnea, was instructed to take meprobamate, 400 mg. four times daily, on Sept. 4, 1957. Physical examination at this time was within normal limits save for tachycardia with a rate of 100 per minute and known labile hypertension with pressures as high as 138/104. A complete blood count one week previously revealed 7000 white blood cells per cubic millimeter, with 57% polymorphonuclear leuko¬ cytes, 2% band forms, 35% lymphocytes, 3% monocytes, and 3% eosinophils; the erythrocyte sedimentation rate was 11 mm. in one hour (Wintrobe) ; hematocrit 46% ; hemoglobin 14.4 gm. per 100 ml. ; total protein 7.72 gm. %, with albumin 4.17 gm. % and globulin 3.55 gm. %. An electro¬ cardiogram was normal, as was a standard posteroanterior roentgenogram of the chest. Ap¬ proximately three hours after ingestion of his first tablet of meprobamate, the patient developed a burning sensation of the forearms and axillary aching. He returned immediately to the clinic and was seen by another physician, who found an erythematous rash of the forearms and urt...
Meprobamate (Miltown, Fquanil) was synthesized in 1950 by Ludwig and Piech in an effort to find a muscle relaxant with longer duration of action and fewer sideeffects than mephenesin.1 In the initial pharmacological evaluation, Berger discov¬ ered three unusual attributes of meproba¬ mate which account in some part for its effectiveness as a tranquilizing agent, name¬ ly: (1) muscle relaxation due to selective blockage of interneuronal synapses bul without effect on monosynaptic reflexes, impulse transmission in peripheral nerves, or activity at the neuromuscular junction ;(2) peculiar "taming" effect on monkeys in that aggression disappears, and (3) thalamic stimulation.2 Although the drug has been in clinical use since 1954, reports of toxicity have been scattered, and only one review of adverse responses has appeared.3 One death has been reported.4 The purpose of this communication is to present a case of meprobamate idiosyncrasy with skin bi¬ opsy and skin testing, to review the pub¬ lished reports to date, and to discuss possible etiologic factors in the pathogene¬ sis of the anaphylactoid reaction.The records of more than 6500 patients have been summarized to date.8"81 Twentythree cases of attempted suicide,6"19 and one hundred thirteen cases of idiosyncrasy have been reported.18"68 Adverse responses to drugs may be con¬ veniently classified into five categories: (1) idiosyncrasy, (2) extension of a therapeu¬ tic effect, (3) allergic reaction, (4) poison¬ ous effect, and, (5) intolerance.82 In Idiosyncrasy.-Many new drugs astound patients and physicians alike by a dramatic but transient disturbance of homeostasis in the form of an anaphylactoid reaction fol¬ lowing ingestion of only one or a few tab¬ lets for the first time. Meprobamate is no exception, since about one patient in 200responds in this fashion, as in the following case report:A 39-year-old white man who had been taking promazine for six weeks without striking benefit because of insomnia, headache, jitteriness, and dyspnea, was instructed to take meprobamate, 400 mg. four times daily, on Sept. 4, 1957. Physical examination at this time was within normal limits save for tachycardia with a rate of 100 per minute and known labile hypertension with pressures as high as 138/104. A complete blood count one week previously revealed 7000 white blood cells per cubic millimeter, with 57% polymorphonuclear leuko¬ cytes, 2% band forms, 35% lymphocytes, 3% monocytes, and 3% eosinophils; the erythrocyte sedimentation rate was 11 mm. in one hour (Wintrobe) ; hematocrit 46% ; hemoglobin 14.4 gm. per 100 ml. ; total protein 7.72 gm. %, with albumin 4.17 gm. % and globulin 3.55 gm. %. An electro¬ cardiogram was normal, as was a standard posteroanterior roentgenogram of the chest. Ap¬ proximately three hours after ingestion of his first tablet of meprobamate, the patient developed a burning sensation of the forearms and axillary aching. He returned immediately to the clinic and was seen by another physician, who found an erythematous rash of the forearms and urt...
Untersuchungen �ber die pr�- und posthepatischen Plasmahistaminkonzentrationen und ihre m�glichen pathophysiologischen Auswirkungen bei Lebercirrhose
Fluorometric estimations of plasma histamine in the peripheral venous blood were performed in a control group of 16 subjects with normal liver values and normal liver biopsy specimen. Two further groups with liver changes were studied: Ten patients with fatty liver (stage I-II) and 22 cases suffering from liver cirrhosis, including 7 patients with portocaval shunt. Additionally, plasma histamine concentrations were determined in the blood of the portal vein, hepatic vein, cubital vein and in the femoral artery of another 11 normal subjects and 8 cirrhotic patients, some of them with portocaval shunt. The elimination of histamine by the liver was calculated. In healthy humans about two thirds (67.8 plus or minus 11.4 per cent; n=11) of the histamine content in the portal vein is eliminated by liver passage. This is due mainly to liver uptake and catabolism of histamine. It could be shown, that the elimination rate (41.0 plus or minus 15.1 per cent, n=8) is diminished in cirrhotic livers. Therefore, the plasma histamine content measured in the peripheral venous blood is significantly higher (p less than 0.001) in cirrhotic patients (1.2 +/- 0.3 ng/ml; n=22) than in healthy subjects (0.7 +/0 0.2 ng/ml; n=16). The expected pathophysiological effects of the elevated plasma histamine levels in liver cirrhosis are discussed with respect to circulatory changes ("hyperdynamic circulation") and their possible role in the development of "hepatogenic" ulcers of the stomach.
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