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. 1969;40(3):425–454.

Codeine and its alternates for pain and cough relief*

3. The antitussive action of codeine—mechanism, methodology and evaluation

Nathan B Eddy, Hans Friebel, Klaus-Jürgen Hahn, Hans Halbach
PMCID: PMC2554640  PMID: 4896168

Abstract

This report—the third of a series on codeine and its alternates for pain and cough relief—presents a detailed review of the physiology and pathophysiology of cough, the methods for the experimental and clinical measurement of the antitussive action of drugs, possible mechanisms of action of antitussive agents, and includes a compilation of experimental results and clinical experience with codeine as an antitussive.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABELMANN W. H., GAENSLER E. A., BADGER T. L. Clinical evaluation of toryn, a new synthetic cough depressant. Dis Chest. 1954 May;25(5):532–541. doi: 10.1378/chest.25.5.532. [DOI] [PubMed] [Google Scholar]
  2. ABRUZZI W. A. Clinical evaluation of levo propoxyphene, a new antitussive. J New Drugs. 1962 Sep-Oct;2:310–313. doi: 10.1177/009127006200200508. [DOI] [PubMed] [Google Scholar]
  3. AMDUR M. O. The influence of aerosols upon the respiratory response of guinea pigs to sulfur dioxide. Am Ind Hyg Assoc Q. 1957 Jun;18(2):149–155. doi: 10.1080/00968205709343484. [DOI] [PubMed] [Google Scholar]
  4. AMLER A. B., ROTHMAN C. B. EVALUATION OF PIPAZETHATE AS AN ANTITUSSIVE AGENT IN PEDIATRIC PRACTICE. J New Drugs. 1963 Nov-Dec;3(6):362–366. doi: 10.1002/j.1552-4604.1963.tb00092.x. [DOI] [PubMed] [Google Scholar]
  5. ARCHIBALD D. W., SLIPP L. B., SHANE S. J. The evaluation of a cough suppressant: an exercise in clinical pharmacology. Can Med Assoc J. 1959 May 1;80(9):734–736. [PMC free article] [PubMed] [Google Scholar]
  6. BALEA T., BURET J. SUR LES PROPRI'ET'ES PHARMACOLOGIQUES DE 2 SELS D'OXOLAMINE. Therapie. 1964 May-Jun;19:631–643. [PubMed] [Google Scholar]
  7. BANYAI A. L., JOANNIDES M., Jr Cough hazard. Dis Chest. 1956 Jan;29(1):52–61. doi: 10.1378/chest.29.1.52. [DOI] [PubMed] [Google Scholar]
  8. BEDELL G. N., SEEBOHM P. M. Treatment of pulmonary emphysema. J Am Med Assoc. 1959 Apr 11;169(15):1699–1702. doi: 10.1001/jama.1959.03000320001001. [DOI] [PubMed] [Google Scholar]
  9. BEECHER H. K. The powerful placebo. J Am Med Assoc. 1955 Dec 24;159(17):1602–1606. doi: 10.1001/jama.1955.02960340022006. [DOI] [PubMed] [Google Scholar]
  10. BEIN H. J., BUCHER K. Anästhetische Wirkung an Lungendehnungsrezeptoren und anderen nervösen Substraten; zur Pharmakologie des Tessalon. Helv Physiol Pharmacol Acta. 1957;15(1):55–62. [PubMed] [Google Scholar]
  11. BENSON W. M., STEFKO P. L., RANDALL L. O. Comparative pharmacology of levorphan, racemorphan and dextrorphan and related methyl ethers. J Pharmacol Exp Ther. 1953 Oct;109(2):189–200. [PubMed] [Google Scholar]
  12. BICKERMAN H. A., BARACH A. L. The experimental production of cough in human subjects induced by citric acid aerosols; preliminary studies on the evaluation of antitussive agents. Am J Med Sci. 1954 Aug;228(2):156–163. doi: 10.1097/00000441-195408000-00005. [DOI] [PubMed] [Google Scholar]
  13. BICKERMAN H. A., COHEN B. M., GERMAN E. The cough response of normal human subjects stimulated experimentally by citric acid aerosol: alterations produced by antitussive agents. I. Methology. Am J Med Sci. 1956 Jul;232(1):57–66. doi: 10.1097/00000441-195607000-00010. [DOI] [PubMed] [Google Scholar]
  14. BICKERMAN H. A., GERMAN E., COHEN B. M., ITKIN S. E. The cough response of healthy human subjects stimulated by citric acid aerosol. II. Evaluation of antitussive agents. Am J Med Sci. 1957 Aug;234(2):191–206. doi: 10.1097/00000441-195708000-00010. [DOI] [PubMed] [Google Scholar]
  15. BICKERMAN H. A., ITKIN S. E. Further studies on the evaluation of antitussive agents employing experimentally induced cough in human subjects. Clin Pharmacol Ther. 1960 Mar-Apr;1:180–191. doi: 10.1002/cpt196012180. [DOI] [PubMed] [Google Scholar]
  16. BIDWELL S. M. R., BOYD E. M. Diphenhydramine hydrochloride, U.S.P. XIV, and respiratory tract fluid. J Pharmacol Exp Ther. 1952 Feb;104(2):224–228. [PubMed] [Google Scholar]
  17. BOISSIER J. R., PAGNY J. [Antitussive action of some phenothiazines]. Therapie. 1960;15:97–102. [PubMed] [Google Scholar]
  18. BOISSIER J. R., PAGNY J. [Comparative experimental action of 3 antitussive agents derived from phenylaminopropane]. Therapie. 1960;15:93–96. [PubMed] [Google Scholar]
  19. BOYD E. M. Expectorants and respiratory tract fluid. Pharmacol Rev. 1954 Dec;6(4):521–542. [PubMed] [Google Scholar]
  20. BUCHER K., JACOT C. Zum Mechanismus des Hustens. Helv Physiol Pharmacol Acta. 1951 Dec;9(4):454–462. [PubMed] [Google Scholar]
  21. BUCHER K. Pathophysiology and pharmacology of cough. Pharmacol Rev. 1958 Mar;10(1):43–58. [PubMed] [Google Scholar]
  22. Boyd E. M., Boyd C. E. Chlophedianol Hydrochloride: A New Antitussive Agent. Can Med Assoc J. 1960 Dec 17;83(25):1298–1301. [PMC free article] [PubMed] [Google Scholar]
  23. CAHEN R., BOUCHERLE A. ETUDE PHARMACOLOGIQUE DE LA NICOTINYLDIHYDROCOD'EINE. C R Seances Soc Biol Fil. 1964;158:1021–1024. [PubMed] [Google Scholar]
  24. CAHEN R., BOUCHERLE A. [Comparative study of some nicotinic esters and some salts of codeine and morpholinoethylmorphine]. C R Seances Soc Biol Fil. 1961;155:1034–1035. [PubMed] [Google Scholar]
  25. CARTER C. H., MALEY M. C. The clinical value of toclase in suppressing the cough reflex. Am J Med Sci. 1957 Jan;233(1):77–79. doi: 10.1097/00000441-195701000-00013. [DOI] [PubMed] [Google Scholar]
  26. CASS L. J., FREDERIK W. S., ANDOSCA J. B. Quantitative comparison of dextromethorphan hydrobromide and codeine. Am J Med Sci. 1954 Mar;227(3):291–296. [PubMed] [Google Scholar]
  27. CASS L. J., FREDERIK W. S. Quantitative comparison of cough-suppressing effects of romilar and other antitussives. J Lab Clin Med. 1956 Dec;48(6):879–885. [PubMed] [Google Scholar]
  28. CASS L. J., FREDERIK W. S. THE CLINICAL EVALUATION OF SILOMAT AS AN ANTITUSSIVE. Curr Ther Res Clin Exp. 1964 Jan;6:14–20. [PubMed] [Google Scholar]
  29. CASS L. J., FREDERIK W. S. The clinical evaluation of sustained release antitussives. Ann Intern Med. 1958 Jul;49(1):151–160. doi: 10.7326/0003-4819-49-1-151. [DOI] [PubMed] [Google Scholar]
  30. CAVALIERI U., NICOLIS F. B., PASQUARIELLO G., QUADRI A., TAMMARO A. E. [Evaluation of the therapeutic activity of antitussive agents in geriatrics]. G Gerontol. 1960 Nov;8:981–988. [PubMed] [Google Scholar]
  31. CHABRIER P., GIUDICELLI R., THUILLIER J. Etude chimique, pharmacologique et clinique d'un nouveau sédatif de la toux: la morpholyléthylmorphine (M.E.M.). Ann Pharm Fr. 1950 Apr;8(4):261–273. [PubMed] [Google Scholar]
  32. CHAKRAVARTY N. K., MATALLANA A., JENSEN R., BORISON H. L. Central effects of antitussive drugs on cough and respiration. J Pharmacol Exp Ther. 1956 Jun;117(2):127–135. [PubMed] [Google Scholar]
  33. CHEN J. Y., BILLER H. F., MONTGOMERY E. G., Jr Pharmacologic studies of a new antitussive, alpha (dimethylaminoethyl)-ortho-chlorobenzhydrol hydrochloride (SL-501, Bayer B-186). J Pharmacol Exp Ther. 1960 Apr;128:384–391. [PubMed] [Google Scholar]
  34. Calesnick B., Christensen J. A. Latency of cough response as a measure of antitussive agents. Clin Pharmacol Ther. 1967 May-Jun;8(3):374–380. doi: 10.1002/cpt196783374. [DOI] [PubMed] [Google Scholar]
  35. DALHAMN T. The determination in vivo of the rate of ciliary beat in the trachea. Acta Physiol Scand. 1960 Jul 15;49:242–250. doi: 10.1111/j.1748-1716.1960.tb01949.x. [DOI] [PubMed] [Google Scholar]
  36. DAVID A., LEITH-ROSS F., VALLANCE D. K. Antitussive and other pharmacological properties of the diethylaminoethoxyethyl ester of alpha alpha-diethylphenylacetic acid, (oxeladin). J Pharm Pharmacol. 1957 Jul;9(7):446–458. doi: 10.1111/j.2042-7158.1957.tb12297.x. [DOI] [PubMed] [Google Scholar]
  37. DE GREGORIO M. [Anti-tussive activity in man and pharmaco-therapeutic characteristics of oxolamine (Perebron)]. Minerva Med. 1960 Dec 1;51:4086–4090. [PubMed] [Google Scholar]
  38. DOMENJOZ R. Zur Auswertung hustenstillender Arzneimittel. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1952;215(1-2):19–24. [PubMed] [Google Scholar]
  39. DOUGLASS B. E. The causes and treatment of cough. Med Clin North Am. 1954 Jul;NEW:949–962. doi: 10.1016/s0025-7125(16)34821-0. [DOI] [PubMed] [Google Scholar]
  40. ENGELHORN R., WELLER E. [Action potentials of respiration-synchronous discharged neurons of the medulla oblongata during coughing]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1961;273:614–635. [PubMed] [Google Scholar]
  41. ENGELHORN R. [Pharmacological research on a new antitussive agent, 1-(p-chlorophenyl)-2,3-dimethyl-4-dimethyl-amino-2-butanol HC1]. Arzneimittelforschung. 1960 Oct;10:785–794. [PubMed] [Google Scholar]
  42. Engelhorn R., Weller E. Zentrale Repräsentation hustenwirksamer Afferenzen in der Medulla oblongata der Katze. Pflugers Arch Gesamte Physiol Menschen Tiere. 1965 Jun 15;284(3):224–239. [PubMed] [Google Scholar]
  43. FRIEBEL H., KUHN H. F. GEWOEHNUNG AN DIE HUSTENHEMMENDE WIRKUNG VON CODEIN. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1964 Mar 19;246:527–537. doi: 10.1007/BF00246306. [DOI] [PubMed] [Google Scholar]
  44. FRIEBEL H., KUHN H. F. [On cough and respiration depressive effect]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1962;243:162–173. [PubMed] [Google Scholar]
  45. FRIEBEL H., REICHLE C., VON GRAEVENITZ A. Zur Hemmung des Hustenreflexes durch zentral angreifende Arzneimittel. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1955;224(4):384–400. [PubMed] [Google Scholar]
  46. FRIEBEL H. [On the cough reflex and its inhibition by pharmacological agents with central effect]. Klin Wochenschr. 1960 Jul 1;38:621–626. doi: 10.1007/BF01485343. [DOI] [PubMed] [Google Scholar]
  47. Friebel H., Hahn K. J. Uber die Variierbarkeit hustenerzeugender Reizströme. Med Pharmacol Exp Int J Exp Med. 1966;14(1):78–86. [PubMed] [Google Scholar]
  48. GLASER J. Allergic disease in general practice. Am Pract Dig Treat. 1961 Oct;12:715–727. [PubMed] [Google Scholar]
  49. GLICK J. Codeine vs. caramiphen in cough control. Del Med J. 1963 Jul;35:180–180. [PubMed] [Google Scholar]
  50. GOSSWALD R. 1-Phenyl-1-(o-chlorphenyl)-3-dimethylamino-propanol-(1), ein neuer hustenhemmender Stoff. Arzneimittelforschung. 1958 Aug;8(8):550–553. [PubMed] [Google Scholar]
  51. GRAHAM J. D. Evaluation of isoaminile citrate as an antitussive. J New Drugs. 1962 Jan-Feb;2:43–49. [PubMed] [Google Scholar]
  52. GRANIER-DOYEUX M., HORANDE M., KUCHARSKI W. [Method for the quantitative evaluation of antitussive agents]. Arch Int Pharmacodyn Ther. 1959 Sep 1;121:287–296. [PubMed] [Google Scholar]
  53. GRAVENSTEIN J. S., BEECHER H. K. Ein Beitrag zur Auswertung hustendämpfender Substanzen am Menschen. Arzneimittelforschung. 1955 Jul;5(7):364–367. [PubMed] [Google Scholar]
  54. GRAVENSTEIN J. S., DEVLOO R. A., BEECHER H. K. Effect of antitussive agents on experimental and pathological cough in man. J Appl Physiol. 1954 Sep;7(2):119–139. doi: 10.1152/jappl.1954.7.2.119. [DOI] [PubMed] [Google Scholar]
  55. GREEN A. F., WARD N. B. The action of analgesics and nalorphine on the cough reflex. Br J Pharmacol Chemother. 1955 Dec;10(4):418–423. doi: 10.1111/j.1476-5381.1955.tb00096.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. HAAS H. Vergleichende Untersuchungen über Analgetica. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1955;225(5):442–452. [PubMed] [Google Scholar]
  57. HAHN L. A., WILBRAND H. The cough alleviating effect of beta-(diphenylmethoxy)-ethyl-trimethylammoniumbromide. Arch Int Pharmacodyn Ther. 1952 Sep 1;91(1-2):144–150. [PubMed] [Google Scholar]
  58. HARA S., YANAURA S. A method of inducing and recording cough and examination of the action of some drugs with this method. Jpn J Pharmacol. 1959 Sep;9:46–54. doi: 10.1254/jjp.9.46. [DOI] [PubMed] [Google Scholar]
  59. HASLREITER E. [The acetycholine cough test as a means of evaluation of a new antitussive agent]. Arzneimittelforschung. 1959 Dec;9:769–773. [PubMed] [Google Scholar]
  60. HENGEN O., KASPAREK H. Husten-hemmende Wirkung einer neuen Substanz. Arzneimittelforschung. 1958 Sep;8(9):620–620. [PubMed] [Google Scholar]
  61. HILLIS B. R. The assessment of cough suppressing drugs. Lancet. 1952 Jun 21;1(6721):1230–1235. doi: 10.1016/s0140-6736(52)92060-6. [DOI] [PubMed] [Google Scholar]
  62. HILLS B. R., KELLY J. C. C. Effect of hexamethonium iodide on lobeline-stimulated coughing. Glasgow Med J. 1951 Mar;32(3):72–76. [PMC free article] [PubMed] [Google Scholar]
  63. HOGLUND N. J., MICHAELSSON M. A method for determining the cough threshold with some preliminary experiments on the effect of codeine. Acta Physiol Scand. 1950 Nov;21(2-3):168–173. doi: 10.1111/j.1748-1716.1950.tb00724.x. [DOI] [PubMed] [Google Scholar]
  64. Hahn K. J., Friebel H. Wirkungen hustenhemmender Pharmaka im zentralen Anteil der Hustenreflexbahn. Med Pharmacol Exp Int J Exp Med. 1966;14(1):87–97. [PubMed] [Google Scholar]
  65. ISBELL H., FRASER H. F. Actions and addiction liabilities of dromoran derivatives in man. J Pharmacol Exp Ther. 1953 Apr;107(4):524–530. [PubMed] [Google Scholar]
  66. KALLQVIST I., MELANDER B. Experimental and clinical evaluation of chlorcyclizine as an antitussive. Arzneimittelforschung. 1957 May;7(5):301–304. [PubMed] [Google Scholar]
  67. KASE Y. Pharmacological studies on cough reflex. 3. Coughing dog and its application. Jpn J Pharmacol. 1955 Mar;4(2):130–135. [PubMed] [Google Scholar]
  68. KASE Y. The coughing dog-an improved method for the evaluation of an antitussive. Pharm Bull. 1954 Sep;2(3):298–299. doi: 10.1248/cpb1953.2.298. [DOI] [PubMed] [Google Scholar]
  69. KELENTEY B., CZOLLNER F., STENSZKY E., MESZAROS Z., SZLAVIK L. Darstellung und pharmakologische Untersuchung einiger morpholylaethylisierter Morphin-Derivate. Arzneimittelforschung. 1958 Jun;8(6):325–330. [PubMed] [Google Scholar]
  70. KELENTEY B., STENSZKY E., CZOLLNER F., SZLAVIK L., MESZAROS Z. Darstellung und pharmakologische Untersuchungen der N-Oxyde der Opium-Alkaloide. Arzneimittelforschung. 1957 Oct;7(10):594–597. [PubMed] [Google Scholar]
  71. KLEIBEL F. EINE NEUE METHODIK DER ELEKTRO-AKUSTISCHEN REGISTRIERUNG VON HUSTENSTOESSEN UND IHRE ANWENDUNG BEI DER OBJEKTIVIERUNG DER WIRKUNG EINIGER ANTITUSSIVA. Med Welt. 1964 Jun 13;24:1317–1320. [PubMed] [Google Scholar]
  72. KLEIN B. The cough sirup as palliative therapy; a clinical evaluation of dimethoxanate. Antibiotic Med Clin Ther (New York) 1958 Jul;5(7):462–465. [PubMed] [Google Scholar]
  73. KONAR N. R., DASGUPTA S. A chemical method for exciting cough reflex in human beings and its use in assessing the effectiveness of cough sedatives. J Indian Med Assoc. 1959 Mar 1;32(5):189–193. [PubMed] [Google Scholar]
  74. KONZETT H. Neuere Gesichtspunkte zur Pharmakologie des Narkotins. Wien Klin Wochenschr. 1955 May 6;67(18):306–309. [PubMed] [Google Scholar]
  75. KONZETT H., ROTHLIN E. Zur Wirkung von Narkotin auf den Hustenreflex und auf die Bronchialmuskulatur. Experientia. 1954 Nov 15;10(11):472–473. doi: 10.1007/BF02170409. [DOI] [PubMed] [Google Scholar]
  76. KRAUSE D. Pharmakologie des alpha(Isopropyl)-alpha-(beta-dimethylaminopropyl)-phenylacetonitril-citrat. Arzneimittelforschung. 1958 Aug;8(8):553–554. [PubMed] [Google Scholar]
  77. KRAUSHAAR A. E., SCHUNK R. W., THYM H. F. EIN NEUES ANTITUSSIVUM: 2-(BETA-HEXAMETHYLENIMINOATHYL)-CYCLOHEXANON-2-CARBONSAUREBENZYLESTER-HCL. Arzneimittelforschung. 1964 Sep;14:986–995. [PubMed] [Google Scholar]
  78. KRUG F. ELEKTROAKUSTISCHE METHODE ZUR OBJEKTIVEN PRUEFUNG DER WIRKUNG VON HUSTENMITTELN. Med Welt. 1964 May 2;18:1026–1028. [PubMed] [Google Scholar]
  79. KUHN H. F., FRIEBEL H. [On the arrangement of the cough impulse into the respiratory rhythm]. Med Exp Int J Exp Med. 1960;3:329–335. [PubMed] [Google Scholar]
  80. LA BARRE J., PLISNIER H. A propos des propriétés antitussigènes et bronchodilatatrices du chlorhydrate de narcotine. Arch Int Pharmacodyn Ther. 1959 Mar 1;119(1-2):205–213. [PubMed] [Google Scholar]
  81. LEVIS S., PREAT S., MOYERSOONS F. [Not Available]. Arch Int Pharmacodyn Ther. 1955 Oct 1;103(2-3):200–211. [PubMed] [Google Scholar]
  82. MAURER H. Die hustenstillende Wirkung von Verbindungen der Dromoran-Reihe. Dtsch Med Wochenschr. 1955 Mar 11;80(10):351–353. doi: 10.1055/s-0028-1116419. [DOI] [PubMed] [Google Scholar]
  83. MAY A. J., WIDDICOMBE J. G. Depression of the cough reflex by pentobarbitone and some opium derivatives. Br J Pharmacol Chemother. 1954 Sep;9(3):335–340. doi: 10.1111/j.1476-5381.1954.tb01689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. MOLL E. L. Observations on the use of papaverine and codeine in general practice. Practitioner. 1953 Jul;171(1021):76–77. [PubMed] [Google Scholar]
  85. MORRIS D. J., SHANE S. J. Human bioassay of a new antitussive agent. Can Med Assoc J. 1960 Nov 19;83:1093–1095. [PMC free article] [PubMed] [Google Scholar]
  86. MULINOS M. G. Antitussive properties of morpholinethyl-morphine (pholcodine). Toxicol Appl Pharmacol. 1960 Nov;2:635–640. doi: 10.1016/0041-008x(60)90081-8. [DOI] [PubMed] [Google Scholar]
  87. MULINOS M. G., NAIR K. G., EPSTEIN I. G. Clinical investigation of antitussive properties of pholcodine. N Y State J Med. 1962 Jul 15;62:2373–2377. [PubMed] [Google Scholar]
  88. NICOLIS F. B., PASQUARIELLO G. Controlled clinical trials of antitussive agents: an experimental evaluation of different methods. J Pharmacol Exp Ther. 1962 May;136:183–189. [PubMed] [Google Scholar]
  89. NICOLIS F. B., PASQUARIELLO G. [Controlled clinical experiments with new antitussive drugs. I. Methodological considerations and evaluation of the antitussive activity of medazonamide]. Clin Ter. 1962 Aug 15;23:215–225. [PubMed] [Google Scholar]
  90. OZAWA H., FUKUDA H., OTSUKI I., CHIBA S. [Antitussive activity and acute toxicity of 2-(2-diethylamino-ethoxy)ethyl alpha,alpha-diethylphenylacetate (oxeladin)]. Yakugaku Zasshi. 1962 Sep;82:1314–1317. [PubMed] [Google Scholar]
  91. PARISH F. A. Clinical evaluation of the antitussive, dimethoxanate. Med Times. 1959 Nov;87:1488–1490. [PubMed] [Google Scholar]
  92. PASQUARIELLO G., NICOLIS F. B. [Controlled clinical experiments with new antitussive drugs. II. Antitussive activity of benzobutamine]. Clin Ter. 1962 Aug 15;23:226–236. [PubMed] [Google Scholar]
  93. PELLMONT B., BACHTOLD H. Pharmakologie des Romilar Roche, einer hustenhemmenden Substanz mit zentralem Angriffspunkt. Schweiz Med Wochenschr. 1954 Dec 4;84(49):1368–1372. [PubMed] [Google Scholar]
  94. PHILLIPS A. M., PHILLIPS R. W., THOMPSON J. L. Chronic cough: analysis of etiologic factors in a survey of 1,274 men. Ann Intern Med. 1956 Aug;45(2):216–231. doi: 10.7326/0003-4819-45-2-216. [DOI] [PubMed] [Google Scholar]
  95. PLISNIER H. A propos des propriétés antitussigènes d'un bromure d'ammonium quaternaire: bromure de 2-triméthylamino-1, 2-diphényldiéthyléther (TDBr). C R Seances Soc Biol Fil. 1958;152(8-9):1267–1268. [PubMed] [Google Scholar]
  96. PLISNIER H., HERNALSTEEN L. Action du chlorhydrate de narcotine sur la sécrétion bronchique. C R Seances Soc Biol Fil. 1959;153(2):363–364. [PubMed] [Google Scholar]
  97. PLISNIER H. [Apropos of the antitussive and xronchoconstrictive properties of tetrahydro-1,4-oxazinylmethyl-codeine (pholcodine)]. C R Seances Soc Biol Fil. 1960;154:451–452. [PubMed] [Google Scholar]
  98. PRIME F. J. The assessment of antitussive drugs in man. Br Med J. 1961 Apr 22;1(5233):1149–1151. doi: 10.1136/bmj.1.5233.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. PRUESSING G. [On experiences with a new type of antitussive medication in postoperative irritative cough]. Dtsch Med J. 1960 Feb 20;11:95–96. [PubMed] [Google Scholar]
  100. RASCH M. Dextrometadons hostlindrande effekt. Nord Med. 1957 Apr 25;57(17):629–631. [PubMed] [Google Scholar]
  101. REICHLE C., FRIEBEL H. Zur Hemmung des Hustenreflexes durch zentral angreifende Arzneimittel. II. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1955;226(6):558–562. [PubMed] [Google Scholar]
  102. ROSIERE C. E., WINDER C. V., WAX J. Ammonia cough elicited through a tracheal side tube in unanesthetized dogs: comparative antitussive bioassay of four morphine derivatives and methadone in terms of ammonia thresholds. J Pharmacol Exp Ther. 1956 Mar;116(3):296–316. [PubMed] [Google Scholar]
  103. ROSS B. B., GRAMIAK R., RAHN H. Physical dynamics of the cough mechanism. J Appl Physiol. 1955 Nov;8(3):264–268. doi: 10.1152/jappl.1955.8.3.264. [DOI] [PubMed] [Google Scholar]
  104. Renovanz H. D., Liebrich K. G. Prüfung von Hustenmitteln, dargestellt am Beispiel von 1-p-Chlorphenyl-2,3-dimethyl-4-dimethylamino-butanol-(2).HCl. Arzneimittelforschung. 1965 Dec;15(12):1393–1411. [PubMed] [Google Scholar]
  105. SALEM H., AVIADO D. M. ANTITUSSIVE DRUGS, WITH SPECIAL REFERENCE TO A NEW THEORY FOR THE INITATION OF THE COUGH REFLEX AND THE INFLUENCE OR BRONCHODILATORS. Am J Med Sci. 1964 May;247:585–600. [PubMed] [Google Scholar]
  106. SALLE J., BRUNAUD M. [New technic for the recording of movement in coughing induced by irritant vapors in the guinea pig]. Arch Int Pharmacodyn Ther. 1960 Jun 1;126:120–125. [PubMed] [Google Scholar]
  107. SCHOFIELD P. B. TRIAL OF DIMYRIL IN GENERAL PRACTICE. Br J Clin Pract. 1963 Oct;17:583–586. [PubMed] [Google Scholar]
  108. SCHROEDER W. Die Verwendung des Vagusschlingenhundes für die Wertbestimmung hustenstillender Substanzen. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1951;212(5-6):433–439. [PubMed] [Google Scholar]
  109. SELL R., LINDNER E., JAHN H. Untersuchungen über die Anaesthesie der Dehnungs- und Berührungsreceptoren durch einige Lokalanaesthetica im Vergleich zur hustenstillenden Wirkung. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1958;234(2):164–178. [PubMed] [Google Scholar]
  110. SEVELIUS H., LESTER P. D., COLMORE J. P. OBJECTIVE EVALUATION OF ANTITUSSIVE AGENTS. Clin Pharmacol Ther. 1965 Mar-Apr;6:146–151. doi: 10.1002/cpt196562146. [DOI] [PubMed] [Google Scholar]
  111. SHANE S. J., KRZYSKI T. K., COPP S. E. Clinical evaluation of a new antitussive agent. Can Med Assoc J. 1957 Sep 15;77(6):600–602. [PMC free article] [PubMed] [Google Scholar]
  112. SILSON J. E. A NEW METHOD FOR EVALUATING ANTITUSSIVE MEDICATIONS USING THE CITRIC ACID CHALLENGE TECHNIQUE. J New Drugs. 1965 Mar-Apr;5(2):94–101. doi: 10.1002/j.1552-4604.1965.tb00231.x. [DOI] [PubMed] [Google Scholar]
  113. SNELL E. S., ARMITAGE P. Clinical comparison of diamorphine and pholcodine as cough suppressants by a new method of sequential analysis. Lancet. 1957 Apr 27;272(6974):860–862. doi: 10.1016/s0140-6736(57)91392-2. [DOI] [PubMed] [Google Scholar]
  114. STEFKO P. L., BENSON W. M. A method for the evaluation of antitussive agents in the unanesthetized dog. J Pharmacol Exp Ther. 1953 Jun;108(2):217–223. [PubMed] [Google Scholar]
  115. Sevelius H., Colmore J. P. Antitussive effect of ethyl dibunate in patients with chronic cough. Clin Pharmacol Ther. 1967 May-Jun;8(3):381–384. doi: 10.1002/cpt196783381. [DOI] [PubMed] [Google Scholar]
  116. Silvestrini B., Pozzatti C. Pharmacological properties of 3-phenyl-5beta diethylaminoethyl-1,2,4-oxadiazole. Br J Pharmacol Chemother. 1961 Jun;16(3):209–217. doi: 10.1111/j.1476-5381.1961.tb01080.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  117. TEDESCHI R. E., TEDESCHI D. H., HITCHENS J. T., COOK L., MATTIS P. A., FELLOWS E. J. A new antitussive method involving mechanical stimulation in unanesthetized dogs. J Pharmacol Exp Ther. 1959 Aug;126:338–344. [PubMed] [Google Scholar]
  118. TIFFENEAU R. The acetylcholine cough test. Dis Chest. 1957 Apr;31(4):404–422. doi: 10.1378/chest.31.4.404. [DOI] [PubMed] [Google Scholar]
  119. TOMORI Z., KNOTZ F., TOMORIOVA K., KLIMA R. [On the effect of vegetative sedation and artificial hypothermia on experimentally induced cough in man]. Anaesthesist. 1960 May;9:169–173. [PubMed] [Google Scholar]
  120. TONER J. J., MACKO E. Pharmacology studies on bis-(1-carbo-beta-diethylaminoethoxy)-1-phenylcyclopentane)-ethane disulfonate. J Pharmacol Exp Ther. 1952 Oct;106(2):246–251. [PubMed] [Google Scholar]
  121. TRENDELENBURG U. Uber die Wirkung einiger Hustenmittel auf Hustenreiz-schwelle und Atmung. Acta Physiol Scand. 1950 Nov;21(2-3):174–186. doi: 10.1111/j.1748-1716.1950.tb00725.x. [DOI] [PubMed] [Google Scholar]
  122. Therapeutic Memoranda. Br Med J. 1879 Apr 12;1(954):545–546. [PMC free article] [PubMed] [Google Scholar]
  123. VAN DONGEN K. The effect of narcotine, ticarda and romilar on coughs and on the movements of the cilia in the air passages. Acta Physiol Pharmacol Neerl. 1956 Mar;4(4):500–507. [PubMed] [Google Scholar]
  124. WIDDICOMBE J. G. Action potentials in vagal efferent nerve fibres to the lungs of the cat. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1961;241:415–432. doi: 10.1007/BF00246686. [DOI] [PubMed] [Google Scholar]
  125. WIDDICOMBE J. G. Receptors in the trachea and bronchi of the cat. J Physiol. 1954 Jan;123(1):71–104. doi: 10.1113/jphysiol.1954.sp005034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. WIDDICOMBE J. G. Respiratory reflexes from the trachea and bronchi of the cat. J Physiol. 1954 Jan;123(1):55–70. doi: 10.1113/jphysiol.1954.sp005033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  127. WIEDEMEIJER J. C., KRAMER H. W., de JONGH D. A screening method for antitussive compounds. Acta Physiol Pharmacol Neerl. 1960;9:501–508. [PubMed] [Google Scholar]
  128. WINDER C. V., WAX J., SERRANO B., SCOTTI L., STACKHOUSE S. P., WHEELOCK R. H. Pharmacological studies of 1,2-dimethyl-3-phenyl-3-propionoxypyrrolidine (CI-427), an analgetic agent. J Pharmacol Exp Ther. 1961 Jul;133:117–128. [PubMed] [Google Scholar]
  129. WINTER C. A., FLATAKER L. Antitussive action of d-isomethadone and d-methadone in dogs. Proc Soc Exp Biol Med. 1952 Nov;81(2):463–465. doi: 10.3181/00379727-81-19912. [DOI] [PubMed] [Google Scholar]
  130. WINTER C. A., FLATAKER L. Antitussive compounds: testing methods and results. J Pharmacol Exp Ther. 1954 Sep;112(1):99–108. [PubMed] [Google Scholar]
  131. WOOLF C. R., ROSENBERG A. OBJECTIVE ASSESSMENT OF COUGH SUPPRESSANTS UNDER CLINICAL CONDITIONS USING A TAPE RECORDER SYSTEM. Thorax. 1964 Mar;19:125–130. doi: 10.1136/thx.19.2.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  132. WOOLF C. R., ROSENBERG A. The cough suppressant effect of heroin and codeine: a controlled clinical study. Can Med Assoc J. 1962 May 5;86:810–812. [PMC free article] [PubMed] [Google Scholar]

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