Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Procarbazine

  • Chapter
Antineoplastic and Immunosuppressive Agents

Abstract

Certain methylhydrazine derivatives constitute a class of antitumor substances whose mechanism of action appears to be different from that of other cytotoxic agents. These compounds were originally tested as monoamine oxidase inhibitors (Zeller et al., 1963; Bollag and Grunberg, 1963) and subsequently were included in a survey for antitumor activity (Bollag, 1963 a; 1964). Systematic variation of substituents on l-methyl-2-benzylhydrazine revealed that antitumor activity was found among those compounds possessing the general formula CH3-NH-NH-CH2R. However, the biological properties of agents within this group showed a marked variation depending on the chemical nature of the R group and an absolute dependency upon the methyl group.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abraham, P., Carbone, P. P., Venditti, J. M.: Evaluation of chemical agents against the plasma cell tumor LPC-1 in mice. Biochem. Pharmacol. 16, 665–673 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Aebi, H., Baggiolini, M., Bickel, M. H., Messiha, F. S.: Untersuchungen über die N-Demethy- lierung des Cytostaticums Ibenzmethyzin (Natulan). Helv. physiol. pharmacol. Acta 24, 1–14 (1966).

    PubMed  CAS  Google Scholar 

  • Aebi, H., Dewald, B., Sitter, H.: Autoxydation N2-substituierter Methylhydrazine; Beeinflussung der Cu- und Fe-Katalyse durch Proteine, Desoxyribonucleinsäure (DNS) und EDTA. Helv. chim. Acta 48, 656 — 674 (1965a).

    Article  CAS  Google Scholar 

  • Aebi, H., Dewald, B., Stjter, H.: Peroxidbildung bei der Autoxydation N2-substituierter Methylhydrazine. Helv. chim. Acta 48, 1380–1394 (1965b).

    Article  PubMed  CAS  Google Scholar 

  • Aebi, H., Suter, H.: Wirkung peroxybildender Cytostatica auf Methaemoglobin- und Glutathiongehalt normaler und akatalatischer Erythrocytes Verh. Schweiz. Ver. Physiol., physiol. Chem., Pharmakol., 65 th Meeting, Lausanne, May 1–2, 1965; Helv. physiol. pharmacol. Acta 23, C9–Cll (1965).

    Google Scholar 

  • Amiel, J.-L., Brezin, C., Sekiguchi, M., Mery, A.-M., Hoerni, B., Garattini, S., Dagttet, G., Mathe, G.: Depression des reactions immunitaires par une methyl hydrazine. Rev. franc. Etud. clin. biol. 9, 636–638 (1964).

    PubMed  CAS  Google Scholar 

  • Baggiolini, M., Bickel, M. H.: Demethylation of ibenzmethyzin (natulan), monomethyl- hydrazine and methylamine by the rat in vivo and by the isolated perfused rat liver. Life Sei. 5, 795–802 (1966).

    Article  CAS  Google Scholar 

  • Baggiolini, M., Bickel, M. H., Messiha, F. S.: Demethylation in vivo of natulan, a tumour- inhibiting methylhydrazine derivative. Experientia (Basel) 21, 334–336 (1965).

    Article  CAS  Google Scholar 

  • Baggiolini, M., Dewald, B.: Induktion und Hemmung der Demethylierung von Ibenzmethyzin (Natulan) und Monomethylhydrazin in der isoliert perfundierten Rattenleber. 68 th Meet. Verhandl. Schweiz. Vereins Physiol., physiol. Chemie Pharmakol., Zürich, Nov. 5, 1966; Helv. physiol. pharmacol. Acta 24, C72–C74 (1966).

    Google Scholar 

  • Baggiolini, M., Dewald, B.: NADPH-dependent oxidation of an alkyl, aralkyl hydrazine to the azo derivative by rat liver microsomes. International Congress on Pharmacology, 4 th, Basel, July 14–18, 1969, pp. 229–230.

    Google Scholar 

  • Baggiolini, M., Dewald, B., Aebi, H.: Oxidation of p-(N1-methylhydrazino methyl)-iV-iso- propyl benzamide (procarbazine) to the methylazo derivative and oxidative cleavage of the N 2 -C bond in the isolated perfused rat liver. Biochem. Pharmacol. 18, 2187 — 2196 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Berneis, K., Bollag, W., Kofler, M., Leuthy, H.: Synergism between ionizing radiation and a cytotoxic methylhydrazine derivative: effect on DNA-degradation. Experientia (Basel) 21, 318–320 (1965).

    Article  CAS  Google Scholar 

  • Berneis, K., Bollag, W., Kofler, M., Leuthy, H.: The enhancement of the after effect of ionizing radiation by a cytotoxic methylhydrazine derivative. Europ. J. Cancer 2, 43–49 (1966).

    Article  CAS  Google Scholar 

  • Berneis, K., Kofler, M., Bollag, W.: Die Auslösung von Fenton-Reaktionen durch cytotoxische Methylhydrazin-Verbindungen. Helv. chim. Acta 47, 1903–1911 (1964).

    Article  CAS  Google Scholar 

  • Berneis, K., Kofler, M., Bollag, W., Kaiser, A., Langemann, A.: The degradation of deoxyribonucleic acid by new tumor inhibiting compounds: the intermediate formation of hydrogen peroxide. Experientia (Basel) 19, 132–133 (1963a).

    Article  CAS  Google Scholar 

  • Berneis, K., Kofler, M., Bollag, W., Zeller, P., Kaiser, A., Langemann, A.: Der pro- oxydative Effect tumorhemmender Methylhydrazin-Verbindungen. Helv. chim. Acta 46, 2157–2167 (1963b).

    Article  CAS  Google Scholar 

  • Bollag, W.: Suppression of the immunological reaction by methylhydrazines, a new class of antitumour agents. Experientia (Basel) 19, 304–305 (1963 a).

    Google Scholar 

  • Bollag, W.: The tumor-inhibitory effects of the methylhydrazine derivative Ro 4-6467/1 (NSC-77213). Cancer Chemother. Rep. 33, 1–4 (1963b).

    PubMed  CAS  Google Scholar 

  • Bollag, W.: Investigations with methylhydrazine derivatives. In: Plattner, P. A. (Ed.): Proceedings of the international symposium on the chemotherapy of cancer, Lugano, April 28–May 1,1964, pp. 191–197. Amsterdam-London-New York: Elsevier 1964.

    Google Scholar 

  • Bollag, W.: Experimental studies with a methylhydrazine derivative — ibenzmethyzin. In: Jelliffe, A. M., Marks, J. (Eds.): Report of the proceedings of the symposium, Downing College, Cambridge, June 22,1965, sponsored by Roche Products Limited; Natulan (Ibenzmethyzin), pp. 1–8. Bristol: John Wright & Sons, Ltd. 1965.

    Google Scholar 

  • Bollag, W., Grunberg, E.: Tumour inhibitory effects of a new class of cytotoxic agents: methylhydrazine derivatives. Experientia (Basel) 19, 130–131 (1963).

    Article  CAS  Google Scholar 

  • Bollag, W., Theiss, E.: Methylhydrazine derivatives. In: Plattner, P.A. (Ed.): Proceedings of the international symposium on the chemotherapy of cancer, Lugano, April 28–May 1, pp. 311–313. Amsterdam-London-New York: Elsevier 1964.

    Google Scholar 

  • Bonadonna, G., Monfardini, S., Oldini, C.: Comparative effects of vinblastine and procarbazine in advanced Hodgkin’s disease. Europ. J. Cancer 5, 393–402 (1969).

    Article  CAS  Google Scholar 

  • Brookes, P.: Studies on the mode of action of ibenzmethyzin. In: Jelliffe, A. M., Marks, J. (Eds.): Report of the proceedings of the symposium, Downing College, Cambridge, June 22, sponsored by Roche Products Limited; Natulan (Ibenzmethyzin), pp. 9–12. Bristol: John Wright & Sons, Ltd. 1965.

    Google Scholar 

  • Brunner, K. W., Young, C. W.: A methylhydrazine derivative in Hodgkin’s disease and other malignant neoplasms. Therapeutic and toxic effects studied in 51 patients. Ann. intern. Med. 63, 69–86 (1965).

    PubMed  CAS  Google Scholar 

  • Carter, S. K. (Ed.): Procarbazine (matulane: NSC-77213): Development and application, Bethesda: Cancer Therapy Evaluation Branch, National Cancer Institute 1970, p. 109. (U.S. Government Printing Office: 1971 0-440-316.)

    Google Scholar 

  • Cerilli, G. J., Gideon, L.: Successful long term inhibition of xenograft rejection. Surg. Forum 20, 284 — 285 (1969).

    PubMed  CAS  Google Scholar 

  • Chabner, B. A., DeVita, V. T., Considine, N., Oliverio, V. T.: Plasma pyridoxal phosphate depletion by the carcinostatic procarbazine. Proc. Soc. exp. Biol. (N. Y.) 132, 1119–1122 (1969).

    Google Scholar 

  • Chaube, S., Murphy, M. L.: The teratogenic effects of 1-methyl-2-para (isopropylcarbamoyl) benzylhydrazine. HCl MH1. Proc. Amer. Ass. Cancer Res. 5, 11 (1964).

    Google Scholar 

  • Chaube, S., Murphy, M. L.: Fetal malformations produced in rats by 2V-isopropyl-a-(2-methyl- hydrazino)-p-toluamide hydrochloride (procarbazine). Teratology 2, 23 — 32 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Colvin, L.B.: Metabolic fate of hydrazines and hydrazides. J. pharm. Sei. 58, 1433–1443 (1969).

    Article  CAS  Google Scholar 

  • DeVita, V.T., Hahn, M. A., Oliverio, V. T.: Monoamine oxidase inhibition by a new carcino- static agent, iV-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). Proc. Soc. exp. Biol. (N.Y.) 120, 561–565 (1965).

    CAS  Google Scholar 

  • DeVita, V. T., Serpick, A., Carbone, P. P.: Combination chemotherapy of advanced Hodgkin’s disease (HD): the NCI program, a progress report. Proc. Amer. Ass. Cancer Res. 10, 19 (1969).

    Google Scholar 

  • DeVita, J. R., Serpick, A. A., Carbone,P.P.: Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Ann. intern. Med. 73, 881–895 (1970).

    PubMed  Google Scholar 

  • Dewald, B., Baggiolini, M., Aebi, H.: N-Demethylation of p-(N1-methylhydrazino methyl)- N-isopropyl benzamide (procarbazine), a cytostatically active methylhydrazine derivative, in the intact rat and in the isolated perfused rat liver. Biochem. Pharmacol. 18, 2179–2186 (1969).

    Google Scholar 

  • Dixon, R. L., Lee, I. P.: Antineoplastic drug effects on spermatogenesis studied by velocity sedimentation cell separation and serial mating. Pharmacologist 13, 294 (1971).

    Google Scholar 

  • Dost, F. N., Reed, D. J.: Methane formation in vivo from 2V-isopropyl alpha(2-methylhydra- zino)-p-toluamide hydrochloride, a tumor-inhibiting methylhydrazine derivative. Biochem. Pharmacol. 16, 1741 — 1746 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Dost, F. N., Reed, D. J., Wang, C. H.: The metabolic fate of monomethylhydrazine and un- symmetrical dimethylhydrazine. Biochem. Pharmacol. 15, 1325–1332 (1966).

    Article  CAS  Google Scholar 

  • Fairley, G. H., Patterson, M. J. L., Scott, R. B.: Chemotherapy of Hodgkin’s disease with cyclophosphamide, vinblastine, and procarbazine. Brit. med. J. 2, 75–78 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Fiorentino, M., Finotto, E.: Action de la procarbazine dans les lymphomes malins. Presse med. 76, 992 (1968).

    Google Scholar 

  • Floersheim, G. L.: Verlängerte Überlebenszeit von Hauthomotransplantaten bei Mäusen durch ein Methylhydrazinderivat. Experientia (Basel) 19, 546–547 (1963).

    Article  CAS  Google Scholar 

  • Floersheim, G. L., Brune, K.: Abstracts of the third international congress of the transplantation society. The Hague 1970.

    Google Scholar 

  • Floersheim, G. L., Tattb, R. N., Phillips-Quagliata, J. M., Levey, R. H.: Induction of tolerance to skin homografts with a methylhydrazine derivative. Synergism with antilymphocytic serum and morphologic responses of the lymphoid system. Agents and Actions 1, 115–123 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Fox, B.W., Fox, M.: Biochemical aspects of the actions of drugs on spermatogenesis. Pharmacol. Rev. 19, 21–57 (1967).

    CAS  Google Scholar 

  • Fusenig, N. E., Obrecht, P., Strickstrock, K. H.: Zur Biochemie der sogenannten cytostati- schen Nebenwirkungen. Vergleichende Untersuchungen. I. Mitteilung: NAD, TP und FDP in Duenndarmschleimhaut, Hoden und Leber nach Trenimon, Velbe und Natulan. Klin. Wschr. 44, 1335–1339 (1966).

    Article  CAS  Google Scholar 

  • Gale, G. R., Simpson, J. G., Smith, A. B.: Studies of the mode of action of iV-isopropyl-a-(2- methylhydrazmo)-p-toluamide. Cancer Res. 27, 1186–1191 (1967).

    PubMed  CAS  Google Scholar 

  • Gelzer, J., Loustalot, P.: Biological and chemotherapeutic studies on primary mammary tumors in C3H and C3HO mice. Int. J. Cancer 2, 179–187 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Grunberg, E., Prince, H. N.: The activity of ibenzmethyzin hydrochloride against the human transplantable tumors human epithelioma No. 3 and human adenoma No. 1. Experientia (Basel) 22, 324–325 (1966).

    Article  CAS  Google Scholar 

  • Grunberg, E., Prince, H. N.: Further studies on the tumor-inhibitory and tumor-inducing properties of N-isopropyl-a-(2-methylhydrazino)-p-toluamide hydrochloride(procarbazine hydrochloride). Chemotherapy 14, 65–76 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Gutterman, J. A., Huang, A. T., Hochstein, P.: Studies on the mode of action of N-isopropyl- a-(2-methylhydrazmo)-p-toluamide (MIH). Proc. Soc. exp. Biol. (N.Y.) 130, 797–802 (1969).

    CAS  Google Scholar 

  • Hilscher, W., Reichelt, P.: Untersuchungen am Samenepithel der Ratte nach Gaben von “Endoxan” und “Natulan”. Beitr. path. Anat. 137, 452–478 (1968).

    CAS  Google Scholar 

  • Huang, A. T., Kremer, W. B.: Inhibition of lymphocyte transformation by an active derivative of MIH. Proc. Amer. Ass. Cancer Res. 10, 41 (1969).

    Google Scholar 

  • Jelliffe, A. M., Marks, J. (Eds.): Natulan (ibenzmethyzin). Bristol: John Wright & Sons, Ltd. 1965.

    Google Scholar 

  • Kelly, M. G., O’Gara,R.W., Gadekar,K., Yancey, S.T., Oliverio,V.T.: Carcinogenic activity of a new antitumor agent, N-isopropyl-a-(2-methyl-hydrazino)-i)-toluamide, hydrochloride (NSC-77213). Cancer Chemother. Rep. 89, 77–80 (1964).

    Google Scholar 

  • Kelly, M. G., O’Gara, R. W., Yancey, S. T., Botkin, C.: Induction of tumors in rats with procarbazine hydrochloride. J. nat. Cancer Inst. 40, 1027–1051 (1968).

    PubMed  CAS  Google Scholar 

  • Kelly, M. G., O’Gara, R. W., Yancey, S. T., Gadekar, K., Botkin, C., Ohverio,V.T.: Comparative carcinogenicity of N-isopropyl-a-(2-methylhydrazino)-p-toluamide HCl (procarbazine hydrochloride), its degradation products, other hydrazines, and isonicotinic acid hydrazide. J. nat. Cancer Inst. 42, 337–344 (1969).

    PubMed  CAS  Google Scholar 

  • Kenis, Y., Werli, J., Hildebrand, J., Tagnon, H. J.: Action d’un dérivé de la methylhydrazine, le Ro 4-6467, dans la maladie de Hodgkin, dans d’autres lymphomes malins et dans des leucémies. Europ. J. Cancer 1, 33–40 (1965).

    Article  CAS  Google Scholar 

  • Kleibel, F.: Untersuchungen mit 3H-markierten Methylhydrazinderivaten. In: Hoffmann, G., Scheer, K. E. (Eds.): Radionuklide in Klin, und Exp. Onkologie; Nuclear-Med. Vol. 2, pp. 63–67 (Suppl. 3 ). Stuttgart: Schattauer 1965.

    Google Scholar 

  • Koblet, H., Diggelmann, H.: On the action of ibenzmethyzin (N-isopropyl-alpha-(2-methyl- hydrazino)-p-toluamide hydrochloride, natulan, IMTH) on protein biosynthesis, p. 344. 9 th International Cancer Congress, Tokyo, Oct. 23–29, 1966.

    Google Scholar 

  • Koblet, H., Diggelmann, H.: Action of ibenzmethyzin (N-isopropyl-a-(2-methyl-hydrazino)- p-toluamid-hydrochlorid, natulan®, IMTH) on protein synthesis in the rat liver. Europ. J. Cancer 4, 45 — 58 (1968).

    Article  CAS  Google Scholar 

  • Kosower, E. M., Kosower, N. S.: Lest I forget thee, glutathione. Nature (Lond.) 224, 117–120 (1969).

    Article  CAS  Google Scholar 

  • Kosower, N. S., Vanderhoff, G. A., Benerofe, B., Hunt, T., Kosower, E. M.: Inhibition of protein synthesis by glutathione disulfide in the presence of glutathione. Biochem. biophys. Res. Comm. 45, 816–821 (1971).

    CAS  Google Scholar 

  • Kreis, W.: Studies on the metabolism and reaction mechanism of a methylhydrazine derivative in BDF P815-leukemic mice. Proc. Amer. Ass. Cancer Res. 7, 39 (1966).

    Google Scholar 

  • Kreis, W.: Metabolism of an antineoplastic methylhydrazine derivative in a P815 mouse neoplasm. Cancer Res. 80, 82–89 (1970).

    Google Scholar 

  • Kreis, W., Burchenal, J. H., Hutchison, D. J.: Influence of a methylhydrazine derivative on the in vivo transmethylation of the S-methyl group of methionine onto purine and pyrimidine bases of RNA. Proc. Amer. Ass. Cancer Res. 9, 38 (1968).

    Google Scholar 

  • Kreis, W., Piepho, S. B., Bernhard, H. V.: Studies of the metabolic fate of the 14C-labeled methyl group of a methylhydrazine derivative in P815 mouse leukemia. Experientia (Basel) 22, 431–433 (1966).

    Article  CAS  Google Scholar 

  • Kreis, W., Yen, W.: An antineoplastic C14-labeled methylhydrazine derivative in P815 mouse leukemia. A metabolic study. Experientia (Basel) 21, 284 — 286 (1965).

    Article  CAS  Google Scholar 

  • Lowenbraun, S., Devita, V. T., Serpick, A. A.: Combination chemotherapy with nitrogen mustard, vincristine, procarbazine and prednisone in lymphosarcoma and reticulum cell sarcoma. Cancer 25, 1018–1025 (1970).

    Article  PubMed  CAS  Google Scholar 

  • MacDonald, A. S., Chan, C. C., Falvey, C. F.: Use of procarbazine hydrochloride (natulan) and procarbazine hydrochloride and azathioprine in canine renal allografts. Transpianation 11, 103–104 (1971).

    Article  CAS  Google Scholar 

  • Makinodan, T., Santos, G. W., Quinn, R. P.: Immunosuppressive drugs. Pharmacol. Rev. 22, 189–247 (1970).

    PubMed  CAS  Google Scholar 

  • Martz, G.: Clinical results with a methylhydrazine derivative. In: Plattner, P. A. (Ed.): Proceedings of the international symposium on the chemotherapy of cancer, Lugano, April 28–May 1, 1964, pp. 198–203. Amsterdam-London-New York: Elsevier 1964.

    Google Scholar 

  • Martz, G., D’Allessandri, A., Keel, H. J.: Preliminary clinical results with a new anti-tumor agent Ro 4-6467. Cancer Chemother Rep. 33, 5–14 (1963).

    PubMed  CAS  Google Scholar 

  • Mathe, G., Berumen, L., Schweisguth, O., Brule, G., Schneider, M., Cattan, A., Amiel, J. L., Schwarzenberg, L.: Methyl-hydrazine in treatment of Hodgkin’s disease. Lancet H, 1077–1080 (1963).

    Google Scholar 

  • Miller, E.: Development of procarbazine. In: Carter, S. K. (Ed.): Procarbazine (matulane: NSC-77213): development and application, pp. 3–8. Bethesda: Cancer Therapy Evaluation Branch, National Cancer Institute 1970.

    Google Scholar 

  • Mortensen, E.: Some effects of l-methyl-2-p-(isopropylcarbamoyl)-benzyl-hydrazine and Mannomustine on the metabolism of human erythrocytes in vitro. Scand. J. Haematol. 2, 288–304 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Obrecht, P., Strickstrock, K.-H., Fusenig, N.: Die Wirkung von Natulan auf den Energiestoffwechsel. Z. Krebsforsch. 69, 25–36 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Obrecht, P., Strickstrock, K. H., Weissleder, H.: Klinische und lymphographische Verlaufskontrollen bei Lymphogranulomatose und Retothelsarkom unter Behandlung mit Natulan. Europ. J. Cancer 2, 59–68 (1966).

    Article  CAS  Google Scholar 

  • Obrecht, P., Strickstrock, K. H., Woekckhaus, J. W.: Zur Frage der biochemischen Wir- kung eines neuen Zytostatikum, Ro 4-6467, aus der KJasse der Methylhydrazinderivate. Chemotherapia 8, 106–113 (1964).

    Article  CAS  Google Scholar 

  • O’Gara, R. W., Adamson, R. H., Kelly, M. G., Dalgard, D. W.: Neoplasma of the hematopoietic system in nonhuman primates: report of one spontaneous tumor and two leukemias induced by procarbazine. J. nat. Cancer Inst. 46, 1121–1130 (1971).

    PubMed  Google Scholar 

  • Oliverio, V. T.: Derivatives of triazenes and hydrazines. In: Holland, J. F., Frei, E., III (Eds.): Cancer medicine. Philadelphia: Lea and Febiger 1973.

    Google Scholar 

  • Oliverio, V. T., Denham, C., DeVita, V. T., Kelly, M. G.: Some pharmacologic properties of a new antitumor agent, JV-isopropyl-a-(2-methylhycLrazino)-p-toluamide, hydrochloride (NSC-77213). Cancer Chemother. Rep. 42, 1–7 (1964).

    PubMed  CAS  Google Scholar 

  • Oliverio, V. T., Kelly, M. G.: Contributions to the biological and clinical effect of a methyl- hydrazine derivative. II. Some preliminary observations on its physiological disposition, antitumor activity and carcinogenicity. In: Plattner, P. A. (Ed.): Proceedings of the international symposium on the chemotherapy of cancer, Lugano, April 28–May 1,1964, pp. 221–227. Amsterdam-London-New York: Elsevier Publishing Co. 1964.

    Google Scholar 

  • Plattner, P. A. (Ed.): Proceedings of the international symposium on the chemotherapy of cancer, Lugano, April 28–May 1, 1964, p. 324. Amsterdam-London-New York: Elsevier 1964.

    Google Scholar 

  • Prough, R., Wittkop, J., Reed, D. J.: Evidence for the hepatic metabolism of some mono- alkylhydrazines. Arch. Biochem. Biophys. 131, 369–373 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Prough, R., Wittkop, J., Reed, D. J.: Further evidence on the nature of microsomal metabolism of procarbazine and related hydrazines. Arch. Biochem. Biophys. 140, 450–458 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Raaflaub, J., Schwartz, D. E.: Uber den Metabolism eines cytostatisch wirksamen Methyl- hydrazin-Derivates (Natulan). Experientia (Basel) 21, 44–45 (1965).

    Article  CAS  Google Scholar 

  • Rao, K. R.: Interaction between the carcinostatic effects of x-rays and ibenzmethyzin on Ehrlich ascites carcinoma in mice. Strahlentherapie 134, 574–584 (1967).

    PubMed  CAS  Google Scholar 

  • Reed, D. J.: Unpublished observations (1971).

    Google Scholar 

  • Reed, D. J., Dost, F. N.: Methane and C02 formation by rats during metabolism of a methyl - hydrazine (natulan). Proc. Amer. Ass. Cancer Res. 7, 57 (1966).

    Google Scholar 

  • Roche Laboratories: Package insert for Matulane capsules by Roche Laboratories Division of Hoffmann-La Roche Inc. Nutley, N. J. August 1969.

    Google Scholar 

  • Rutishattser, A., Bollag, W.: Cytological investigations with a new class of cytotoxic agents: methylhydrazine derivatives. Experientia (Basel) 19, 131–132 (1963).

    Article  Google Scholar 

  • Samuels, M. L., Leary, W. V., Alexanian, R., Howe, C. D., Frei, E., III: Clinical trials with N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide hydrochloride in malignant lymphoma and other disseminated neoplasia. Cancer 20, 1187–1194 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Sartorelli, A. C., Creasey, W. A.: Cancer chemotherapy. Ann. Rev. Pharmacol. 9, 51–72 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Sartorelli, A. C., Tsunamura, S.: Metabolic alterations in L5178Y lymphoma cells induced by N-isopropy 1–α - (2 - methy lhy dr az ino) p-toluamide. Proc. Amer. Ass. Cancer Res. 6, 55 (1965).

    Google Scholar 

  • Sartorelli, A. C., Tsunamttra, S.: Studies on the biochemical mode of action of a cytotoxic methylhydrazine derivative, N-isopropyl-a-(2-methylhydrazino)-p-toluamide. Molec. Pharmacol. 2, 275–283 (1966).

    CAS  Google Scholar 

  • Schwartz, D. E.: Comparative metabolic studies with natulan, methylhydrazine and methyl - amine in rats. Experientia (Basel) 22, 212–213 (1966).

    Article  CAS  Google Scholar 

  • Schwartz, D. E., Bollag, W., Obrecht, P.: Distribution and excretion studies of procarbazine in animals and man. Arzneimittel-Forsch. 17, 1389–1393 (1967 c).

    Google Scholar 

  • Schwartz, D. E., Brubacher, G. B., Vecchi, M.: Metabolic formation of methane from N- methyl-substituted hydrazine compounds and carcinostatic activity. J. labelled Compounds 111, 487–488 (1967a).

    Google Scholar 

  • Schwartz, D.E., Brubacher, G. B., Vecche, M.: Metabolic formation of methane from N- methyl-substituted hydrazine compounds and carcinostatic activity, pp. 65–66. International conference on the use of radioactive isotopes in pharmacology, Geneva, Sept. 20–23 (1967b).

    Google Scholar 

  • Stewart, P. B., Bell,R.: Procarbazine as an immunosuppressant in animals. J. Immunology 105, 1271–1277 (1970).

    CAS  Google Scholar 

  • Stewart, P. B., Cohen, V.: Antiserum to lymphocytes and procarbazine compared as immunosuppressants in mice. Science 164, 1082–1083 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Stock, J. A.: Other antitumor agents. Exp. chemotherapy 5, 333–416 (1967).

    CAS  Google Scholar 

  • Todd, I. D. H.: Natulan in management of late Hodgkin’s disease, other lymphoreticular neoplasms, and malignant melanoma. Brit. med. J. 1, 628–631 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Tsuji, T., Kosower, E. M.: Diazenes, VI. Alkyldiazenes. J. Amer. chem. Soc. 93, 1992–1999 (1971).

    Google Scholar 

  • Weitzel, G. L., Schneider, F., Fretzdokff, A. M.: Cytostatischer Wirkungsmechanismus der Methylhydrazine. Experientia (Basel) 20, 38–39 (1964a).

    Article  CAS  Google Scholar 

  • Weitzel, G. L., Schneider, F., Fretzdorff, A. M.,Durst, J., Hirsohmann, W.: Untersuchungen zum cytostatischen Wirkungsmechanismus der Methylhydrazine, II. Z. Physiol. Chem. 348, 433–442 (1967).

    Google Scholar 

  • Weitzel, G. L., Schneider, F., Fretzdorff, A. M., Seynsche, K., Finger, H.: Untersuchungen zum cytostatischen Wirkungsmechanismus der Methylhydrazine. Z. Physiol. Chem. 336, 271–282 (1964b).

    Article  CAS  Google Scholar 

  • Weitzel, G. L., Schneider, F., Kummer, D., Ochs, H.: Cytostatischer Wirkungsmechanismus von Natulan. Z. Krebsforsch. 70, 354–365 (1968).

    PubMed  CAS  Google Scholar 

  • Wittkop, J. A., Prough, R. A., Reed, D. J.: Oxidative demethylation of JV’-methylhydrazines by rat liver microsomes. Arch. Biochem. Biophys. 134, 308–315 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Zeller, P., Gutmann, H., Hegedus,B., Kaiser, A., Langemann, A., Mueller, M.: Methylhydrazine derivatives, a new class of cytotoxic agents. Experientia (Basel) 19, 129 (1963)

    Google Scholar 

Download references

Authors
  1. Donald J. Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, Yale University School of Medicine, 06510, New Haven, Connecticut, USA

    Alan C. Sartorelli (Professor) (Professor)

  2. Laboratory of Chemical Pharmacology, National Cancer Institute, National Institutes of Health, 20014, Bethesda, Maryland, USA

    David G. Johns M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1975 springer-Verlag Berlin-Heidelberg

About this chapter

Cite this chapter

Reed, D.J. (1975). Procarbazine. In: Sartorelli, A.C., Johns, D.G. (eds) Antineoplastic and Immunosuppressive Agents. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 38 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65806-8_41

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-65806-8_41

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-65808-2

  • Online ISBN: 978-3-642-65806-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation