Tryparsamide

Abstract: ‘MELARSEN’ (disodium - p - melaminylphenylarsonate1, I) is active against tryparsamide-resistant trypanosome strains both in the field2 and in the laboratory3, and is more effective than tryparsamide (sodium p-glycineamidophenylarsonate) in rendering trypanocidal the cerebrospinal fluid in rabbits4. In view of these properties, the behaviour of a ‘Melarsen’-resistant trypanosome strain seemed to merit investigation.

Abstract: Summary 1. Strains of trypanosomes are to be found in the French Cameroun which are resistant to tryparsamide only, or in addition to tryparsamide, to one, or several drugs of the group tartar emetic, orsanine, amidines, moranyl. 2. Ninety seven per cent out of 394 tryparsamide resistant patients responded favorably to treatments with Mel B; three per cent were Mel B resistant. 3. Mel B resistance occurs in the French Cameroun under two circumstances: (a) linked to tryparsamide resistance as an inherent character of certain strains of trypanosomes; (b) developed in the organism of infested humans, in the wake of an insufficient treatment with a compound containing the same phenylmelaminyl radical, as Mel B.

Abstract: The present study of the action of tryparsamide in human trypanosomiasis concludes a series of chemical and biological investigations in a particular problem of chemotherapy and thus represents the final step in a logical method of approach to such a problem. It has been shown that tryparsamide, the sodium salt of N-phenylglycineamide-p-arsonic acid, possesses a marked trypanocidal activity in human trypanosomiasis caused by Tr. gambiense. Single doses of from 0.5 to 5.0 gm. produced a peripheral sterilization of lymph glands and blood in an average of 6 to 12 hours. The duration of the peripheral sterilization following single doses of 17 to 83 mg. per kilo ranged from 17 to 58 days in patients who ultimately showed a return of trypanosomes to the peripheral blood. In a number of patients, however, treated with single doses of 9 to 68 mg. per kilo, no such relapse was detected during an observation period of from 40 to 111 days. The drug is extremely soluble in water and may be administered intramuscularly as well as intravenously. The immediate trypanocidal action after intramuscular administration was as rapid as that following the intravenous route while the duration of peripheral sterilization was appreciably longer. Relatively few repeated doses produced in advanced cases a marked and rapid diminution of the cells of the spinal fluid and were associated with definite improvement of mental and nervous symptoms. The occurrence of visual disturbances in certain advanced cases was the only untoward effect detected during the course of the work, and was apparently related to a too frequent administration of the drug. The condition was transitory in the majority of instances and resumption of treatment was not followed by a recurrence of this symptom. The general beneficial effect of the drug was a noticeable feature of its action in both early and advanced cases as shown by the disappearance of subjective symptoms, by the return of the pulse and temperature to normal limits, by the pronounced improvement of the blood picture, and by well marked gains in weight.

Abstract: The natural form of blackhead, although very fatal to young turkeys, is favorably influenced by treatment with certain of the newer arsenical compounds. Neoarsphenamine injected intravenously in toxic doses has a somewhat favorable effect on the course of the spontaneous disease and evidently lowers the mortality. Its instability, its pronounced toxicity for young turkeys, as well as the difficulty of obtaining amounts suitable for the cases to be treated on any one occasion, serve to make its employment impracticable. Less favorable results were obtained with atoxyl. Arsenious acid fed daily in small doses failed to prevent blackhead and possibly increased the incidence of infection. In larger doses it failed to cure spontaneous blackhead. Tryparsamide may be injected in cases of spontaneous blackhead in doses as high as 1 gm. per kilo of body weight either intravenously or subcutaneously without serious toxic effect. Prompt clinical improvement usually follows and the mortality is undoubtedly greatly lowered. With inoculated blackhead recovery is more difficult to obtain. Birds treated by injections of either neoarsphenamine or atoxyl failed to recover. There were two recoveries among three tryparsamidetreated cases. An attempt to cure inoculated blackhead at an advanced stage by the injection of tryparsamide failed. The study of the lesions of treated turkeys shows that tryparsamide, and to some extent neoarsphenamine, have a more pronounced effect on the liver lesions than on the disease in the lung, which accounts for the discrepancy in the results of the treatment of spontaneous and inoculated blackhead. There is histological evidence of prompt absorption of necrotic liver parenchyma; moreover, the protozoa are destroyed more rapidly in the liver than in the lung. Tryparsamide has the most pronounced curative action on blackhead infection of any of the drugs thus far tested. Either intravenous or subcutaneous injection of appropriate doses of this drug at the first appearance of symptoms should serve to cure the majority of cases of blackhead.