Skip to main content
SpringerLink
Log in
Book cover

Antimalarial Drugs I pp 351–373Cite as

Preclinical Testing

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 68))

Abstract

Since the establishment of the United States Army Antimalarial Drug Development Programme in 1963, there has been a continual evolution of the organisational structure, the philosophy, the approach and the methods used. This evolution reflects the rapid development of science and technology in these years, the gradual development of a multidisciplinary cadre of scientists and the evolution of ethical principles and statutory requirements. The philosophy, approaches and methods which will be discussed in this chapter are those which have been employed by the US Army Programme in the past, those which are presently being employed and those which will be incorporated in the future. As the science and technology of drug development continue to evolve, more rational and more efficient methods must be developed and applied to malaria research, to ensure the optimal use of the limited resources which have traditionally been allocated to this disease.

The authors dedicate this chapter to the late Dr. Robert S. Rozman, who devoted most of his later years to the development of antimalarial drugs

This is a preview of subscription content, 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   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ames BN, McCann J, Yamasaki E (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res 31:347–363

    Article  PubMed  CAS  Google Scholar 

  • Arora RB, Madan BR, Patnak RK (1956) Antiarrhythmics: Part VIII: Chloroquine, amodiaquine, procaine amide, and quinidine in experimental auricular arrhythmias simulating clinical disorders. Indian J Med Res 44:453–462

    PubMed  CAS  Google Scholar 

  • Bass SW, Ramirez MA, Aviado DM (1972) Cardiopulmonary effects of antimalarial drugs. VI. Adenosine, quinacrine, and primaquine. Toxicol Appl Pharmacol 21:464–481

    Article  PubMed  CAS  Google Scholar 

  • Bigger JT Jr, Hoffman BF (1980) Antiarrhythmic drugs. In: Gilman AG, Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. McMillan, New York, p 768

    Google Scholar 

  • Caldwell RW, Nash CB (1977) Pulmonary and cardiovascular effects of mefloquine methanesulfonate. Toxicol Appl Pharmacol 40:437–448

    Article  PubMed  CAS  Google Scholar 

  • Caldwell RW, Nash CB (1978) Cardiopulmonary effects of IV quinine HCl(Q). Fed Proc 37:689

    Google Scholar 

  • Canfield CJ, Heiffer MH (1978) The US Army drug development program. In: Adolphe M (ed) Advances in pharmacology and therapeutics, vol 10, Chemotherapy. Oxford, New York, pp 99-108

    Google Scholar 

  • Cenedella RJ, Saxe LH (1967) Automated mass screening of compounds for antimalarial activity. Automation in analytical chemistry. Technicon symposium. Technicon Corporation, New York, pp 281-285

    Google Scholar 

  • Cenedella RJ, Saxe LH, Van Dyke K (1970) An automated method of mass drug testing applied to screening for antimalarial activity. Chemotherapy 15:158–176

    Article  PubMed  CAS  Google Scholar 

  • Coatney GR, Cooper LC, Eddy NB, Greenberg J (1953) Survey of antimalarial agents. Chemotherapy of Plasmodium gallinaceum infections: Toxicity; correlation of structure and action. Public health monograph number 9, US Government Printing Office, Washington, DC

    Google Scholar 

  • Coatney GR, Collins WE, Warren M, Contacos PG (1971) The primate malarias. US Department of Health, Education and Welfare Publication, US Government Printing Office, Washington, DC

    Google Scholar 

  • Davey DG (1963) Chemotherapy of malaria. Biological basis of testing methods. In: Schnitzer RJ, Hawkin F (eds) Experimental Chemotherapy. Academic, New York, p 487

    Google Scholar 

  • Davidson DE, Johnson DO, Tanticharoenyos P, Hickman RL, Kinnamon KE (1976) Evaluating new antimalarial drugs against trophozoite-induced Plasmodium cynomolgi malaria in rhesus monkeys. Am J Trop Med Hyg 25:26–33

    PubMed  CAS  Google Scholar 

  • Davidson DE, Ager AL, Brown JL, Chappie FE, Whitmire RE, Rossan RN (1981) New tissue schizonticidal antimalarial drugs. Bull WHO 59:463–479

    PubMed  CAS  Google Scholar 

  • Desjardins RE, Canfield CJ, Haynes JD, Chulay JD (1979) Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother 16:710–718

    Article  PubMed  CAS  Google Scholar 

  • DiPalma JR (1971) Chemotherapy of protozoan infections 1: Malaria. In: DiPalma JR (ed) Drill’s Pharmacology in Medicine, McGraw-Hill, New York, p 1783

    Google Scholar 

  • Ferone R, Burchall JJ, Hitchings GH (1969) Plasmodium berghei dihydrofolate reductase. Isolation, properties, and inhibition by antifolates. Mol Pharmacol 5:49–59

    PubMed  CAS  Google Scholar 

  • Finney DJ (1971) Probit Analysis. Cambridge University Press, Cambridge

    Google Scholar 

  • Genther CS, Smith CC (1977) Antifolate studies. Activities of 40 potential antimalarial compounds against sensitive and chlorguanide triazine resistant strains of folate-requiring bacteria and Escherichia coli. J Med Chem 20:237–243

    Article  PubMed  CAS  Google Scholar 

  • Genther CS, Squires W, Fradkin R, Schmidt LH (1948) Malaria chemotherapy: 1. The response of trophozoite-induced infections with Plasmodium cynomolgi to various antimalarial drugs. Fed Proc 7:221

    PubMed  CAS  Google Scholar 

  • Gerberg EJ (1971) Evaluation of antimalarial compounds in mosquito test systems. Trans R Soc Trop Med Hyg 65:358–363

    Article  PubMed  CAS  Google Scholar 

  • Gregory KG, Peters W (1970) The chemotherapy of rodent malaria. IX. Causal prophylaxis, I: A method for demonstrating drug action on exo-erythrocytic stages. Ann Trop Med Parasitol 65:15–24

    Google Scholar 

  • Grund P, Andose JD, Rhodes JB, Smith GM (1980) Three-dimensional molecular modeling and drug design. Science 208:1425–1431

    Article  Google Scholar 

  • Haynes JD, Diggs CL, Hines FA, Desjardins RE (1976) Culture of human malaria parasites Plasmodium falciparum. Nature 263:767–769

    Article  PubMed  CAS  Google Scholar 

  • Hemwall E, DiPalma JR (1979) Cardiovascular and antiarrhythmic effects of mefloquine. Pharmacologist 21:200

    Google Scholar 

  • Jiang JB (1978) Plasmodium: Experimental animals for human malaria and research needs. A review. Exp Parasitol 46:339–352

    Article  PubMed  CAS  Google Scholar 

  • Killick-Kendrick R, Peters W (1978) Rodent malaria. Academic, New York

    Google Scholar 

  • Kinnamon KE, Rothe WE (1975) Biological screening in the US Army antimalarial drug development program. Am J Trop Med Hyg 24:174–178

    PubMed  CAS  Google Scholar 

  • Korte DW Jr, Herman A, Neidig MH Jr, Heiffer MH (1978) Cardiovascular activity of the candidate antimalarial drug (1-t-butyl)-2-(t-butylaminomethyl)-6-(4-chlorophenyl)-phenol phosphate (WR 194965 H3PO4) in the dog. Pharmacologist 20:253

    Google Scholar 

  • Lee CC, Kowalski JJ, Kintner LD, Hong CB, Girven JD, Ellis ER (1977) Subacute oral toxicity of 4-(t-butyl)-2-(t-butylaminomethyl)-6-(4-chlorophenyl)phenol phosphate, WR 194965H 3 PO 4sc, in dogs. Supplement to interim report No. 113, Midwest Research Institute, Kansas City, MO. USAMRDC Contract DAMD 17-74-C-4036

    Google Scholar 

  • Marshall RJ, Ojewole JA (1978) Comparative effects of some antimalarial drugs on isolated cardiac muscle of the guinea pig. Toxicol Appl Pharmacol 46:757–768

    Article  Google Scholar 

  • Mecca TE, Elam JT, Nash CB, Caldwell RW (1980) alpha-Adrenergic blocking properties of quinine HCl. Eur J Pharmacol 63:159–166

    Article  PubMed  CAS  Google Scholar 

  • Merkli B, Peters W (1976) A comparison of two different methods for the selection of primaquine resistance in Plasmodium berghei berghei. Ann Trop Med Parasitol 70:473–474

    PubMed  CAS  Google Scholar 

  • Moe GK, Peralta B, Seevers MH (1949) Central impairment of sympathetic reflexes by 8-aminoquinolines. J Pharmacol Exp Ther 95:407–414

    PubMed  CAS  Google Scholar 

  • Most H, Montuori WA (1975) Rodent systems (Plasmodium berghei-Anopheles stephensi) for screening compounds for potential causal prophylaxis. Am J Trop Med Hyg 24:179–182

    PubMed  CAS  Google Scholar 

  • Osdene TS, Russell PB, Rane L (1967) 2,4,7-Triamino-6-ortho-substituted arylpteridines. A new series of potent antimalarial agents. J Med Chem 10:431–434

    Article  PubMed  CAS  Google Scholar 

  • Peters W (1965 a) Drug resistance in Plasmodium berghei Vincke and Lips, 1948. I. Chloroquine resistance. Exp Parasitol 17:80–89

    Article  PubMed  CAS  Google Scholar 

  • Peters W (1965 b) Drug resistance in Plasmodium berghei Vincke and Lips, 1948. II. Triazine resistance. Exp Parasitol 17:90–96

    Article  PubMed  CAS  Google Scholar 

  • Peters W (1966) Drug responses of mepacrine-and primaquine-resistant strains of Plasmodium berghei Vincke and Lips, 1948. Ann Trop Med Parasitol 60:25–30

    PubMed  CAS  Google Scholar 

  • Peters W (1968) The chemotherapy of rodent malaria, V. Dynamics of drug resistance, Part I: Methods for studying the acquisition and loss of resistance to chloroquine by Plasmodium berghei. Ann Trop Med Parasitol 62:277–287

    PubMed  CAS  Google Scholar 

  • Peters W (1970) Chemotherapy and drug resistance in malaria. Academic, New York

    Google Scholar 

  • Peters W (1974) Prevention of drug resistance in rodent malaria by the use of drug mixtures. Bull WHO 51:379–383

    PubMed  CAS  Google Scholar 

  • Peters W, Portus J, Robinson BL (1977) The chemotherapy of rodent malaria, XXVIII. The development of resistance to mefloquine (WR 142490). Ann Trop Med Parasitol 71:419–427

    PubMed  CAS  Google Scholar 

  • Rane DS, Kinnamon KE (1979) The development of a “high volume tissue schizonticidal drug screen” based upon mortality of mice inoculated with sporozoites of Plasmodium berghei. Am J Trop Med Hyg 23:937–947

    Google Scholar 

  • Rane L, Rane DS (1972) A screening procedure, based on mortality, with sporozoite-induced Plasmodium gallinaceum malaria in chicks. Proc Helminthol Soc Wash 39:283–287

    Google Scholar 

  • Rieckmann KH, McNamara JV, Frischer H, Stuckert TA, Carson PE, Powell RD (1968) Effects of chloroquine, quinine, and cycloguanil upon the maturation of asexual erythrocytic forms of two strains of Plasmodium falciparum in vitro. Am J Trop Med Hyg 17:661–671

    PubMed  CAS  Google Scholar 

  • Rossan RN, Young MD, Baerg DC (1975) Chemotherapy of Plasmodium vivax in Saimiri and Aotus models. Am J Trop Med Hyg 24:168–173

    PubMed  CAS  Google Scholar 

  • Rothe WE, Jacobus DP (1968) Laboratory evaluation of the phototoxic potency of quinolinemethanols. J Med Chem 11:366–368

    Article  PubMed  CAS  Google Scholar 

  • Rothe WE, Jacobus DP, Walter WG (1969) Treatment of trophozoite-induced Plasmodium knowlesi infection in the rhesus monkey with trimethoprim and sulfalene. Am J Trop Med Hyg 18:491–494

    PubMed  CAS  Google Scholar 

  • Schmidt LH (1973) Infections with Plasmodium falciparum and Plasmodium vivax in the owl monkey — model systems for basic biological and chemotherapeutic studies. Trans R Soc Trop Med Hyg 67:446–474

    Article  PubMed  CAS  Google Scholar 

  • Schmidt LH (1978 a) Plasmodium falciparum and Plasmodium vivax infections in the owl monkey (Aotus trivirgatus). I. The courses of untreated infections. Am J Trop Med Hyg 27:671–702

    PubMed  CAS  Google Scholar 

  • Schmidt LH (1978 b) Plasmodium falciparum and Plasmodium vivax infections in the owl monkey (Aotus trivirgatus). II. Responses to chloroquine, quinine, and pyrimethamine. Am J Trop Med Hyg 27:703–717

    PubMed  CAS  Google Scholar 

  • Schmidt LH (1978 c) Plasmodium falciparum and Plasmodium vivax infections in the owl monkey (Aotus trivirgatus). III. Methods employed in the search for new blood schizontocidal drugs. Am J Trop Med Hyg 27:718–737

    PubMed  CAS  Google Scholar 

  • Schmidt LH, Rossan RN, Fisher KF (1963) The activity of a repository form of 4,6-diamino-1(p-chlorophenyl)-1,2-dihydro-2,2-dimethyl-s-triazine against infections with Plasmodium cynomolgi. Am J Trop Med Hyg 12:494–503

    PubMed  CAS  Google Scholar 

  • Schüpbach ME (1979) Mutagenicity evaluation of the two antimalarial agents chloroquine and mefloquine, using a bacterial fluctuation test. Mutat Res 68:41–49

    Article  PubMed  Google Scholar 

  • Terzian LA (1947) A method for screening antimalarial compounds in the mosquito host. Science 106:449–150

    Article  PubMed  CAS  Google Scholar 

  • Terzian LA, Stahler N, Weathersby AB (1949) The action of antimalarial drug in mosquitoes infected with Plasmodium gallinaceum. J Infect Dis 84:47–55

    Article  PubMed  CAS  Google Scholar 

  • Thompson PE, Werbel LM (1972) Antimalarial agents: Chemistry and pharmacology. In: DeStevens G (ed) Medicinal Chemistry: A series of monographs, vol 12. Academic, New York

    Google Scholar 

  • Thompson PE, Olszewski BJ, Elslager EF, Worth DF (1963) Laboratory studies on 4,6-diamino-1-(p-chlorophenyl)-1,2-dihydro-2,2-dimethyl-s-triazine pamoate (CI-501) as a repository antimalarial drug. Am J Trop Med Hyg 12:481–493

    PubMed  CAS  Google Scholar 

  • Thompson PE, Bayles A, Olszewski B, Waitz JA (1965) Qunine-resistant Plasmodium berghei in mice. Science 148:1240–1241

    Article  PubMed  CAS  Google Scholar 

  • Thompson PE, Olszewski B, Bayles A, Waitz JA (1967) Relations among antimalarial drugs: Results of studies with cycloguanil-, sulfone-, or chloroquine-resistant Plasmodium berghei in mice. Am J Trop Med Hyg 16:133–145

    PubMed  CAS  Google Scholar 

  • Trager W, Jensen JB (1976) Human malaria parasites in continuous culture. Science 193:673–675

    Article  PubMed  CAS  Google Scholar 

  • Wiselogle FY (1946) A survey of antimalarial drugs, 1941–1945. J. W. Edwards, Ann Arbor, MI

    Google Scholar 

  • World Health Organization (1971) Report of conference on procedures for screening potential antimalarial compounds. WHO Document WHO/MAL 72:763

    Google Scholar 

  • World Health Organization (1973) Chemotherapy of malaria and resistance to antimalarials. WHO Tech Rep Ser 529

    Google Scholar 

  • Young MD, Baerg DC, Rossan RN (1975) Parasitological reviews. Experimental monkey hosts for human plasmodia. Exp Parasitol 38:136–152

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. M. H. Heiffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. E. Davidson Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. W. Korte Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, Great Britain

    Wallace Peters M.D., DSc, FRCP, DTM & H (Professor of Medical Protozoology) (Professor of Medical Protozoology)

  2. Scientific Advisory Services, Wellcome Research Laboratories, Ravens Lane, Berkhamsted, Herts, HP4 2DY, Great Britain

    William H. G. Richards BSc, Ph.D. (Manager) (Manager)

Rights and permissions

Reprints and permissions

Copyright information

© 1984 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Heiffer, M.H., Davidson, D.E., Korte, D.W. (1984). Preclinical Testing. In: Peters, W., Richards, W.H.G. (eds) Antimalarial Drugs I. Handbook of Experimental Pharmacology, vol 68. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-35326-4_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-35326-4_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-34991-5

  • Online ISBN: 978-3-662-35326-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation