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Downloaded for Personal Non-Commercial Research Or Study, Without Prior Permission Or Charge https://theses.gla.ac.uk/ Theses Digitisation: https://www.gla.ac.uk/myglasgow/research/enlighten/theses/digitisation/ This is a digitised version of the original print thesis. Copyright and moral rights for this work are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This work cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Enlighten: Theses https://theses.gla.ac.uk/ [email protected] THE MODE OF ACTION Off SOME DRUGS AND CHEMICALS USED TO TREAT HYPERTENSION, OR AS MUSCLE RELAXANTS A Thesis submitted to the University of Glasgow in candidature for the degree of Doctor of Philosophy in the Faculty of Medicine Uy KAMALUDDIN AHMAD, M.B.3.S. (Dacca) Experimental Pharmacology Division, Institute of Physiology, and Department of Materia Medica and Therapeutics, September, 14th 1961 The University of Glasgow, ProQuest Number: 10656196 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Pro ProQuest 10656196 Published by ProQuest LLC(2017). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 . CONTENTS Acknowledgements........................ ............. ix List of publications and communication..... .*xi PART I Studies on the effect of certain drugs upon the flux of calcium, potassium and sodium ions in skeletal muscle. Chapter I. ‘ Introduction.......................... 1 Chapter II. A. Materials........ 80 B. Experimental, 1. Investigation of the effect of drugs on calcium-47 uptake by isolated frog sartorius muscle...... 82 2. Investigation of the effect of drugs on potassium-42 uptake by isolated frog sartorius.muscle.... 86 3. Investigation of the effect of drugs on sodium-24 uptake by isolated frog sartorius muscle......88 4. Investigation of the effect of drugs on calcium-47 release from isolated frog sartorius muscle.... 90 5. Investigation of the effect of drugs on potassium-42 release from isolated frog sartorius muscle.... 91 J C. Statistical Analysis.............•....... 93 Chapter III. Results. Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of suxamethonium.... 96 Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of decamethonium.... 98 'Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of nicotine. ••»»•••• ^0 Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of ryanodine...... 103 Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of carbachol...... 105 Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of neostigmine.... 107 Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of edrophonium...... 109 Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of tubocurarine.. ...H2 - ii - f Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of gallamine........ 114 Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of protoveratrine A., 116 Uptake of calcium-47, potassium-42 and sodium-24 by isolated frog sartorius muscle in the presence of protoveratrine B., 119 Effect of suxamethonium on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle.............. 121 Effect of decamethonium on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle....... ,,,*•» 124 Effect of nicotine on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle............ 127 Effect of ryanodine on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle • •..... 127 Effect of carbachol on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle,........... 130 Effect of neostigmine on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle,. ......... 133 - iii - T w Effect of edrophonium on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle......... 136 Effect of tubocurarine on the release of calcium-47 and potassium-42 from . isolated frog sartorius muscle.............. 136 Effect of gallamine on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle 141 Effect of protoveratrine A on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle.............. 146 Effect of protoveratrine B on the release of calcium-47 and potassium-42 from isolated frog sartorius muscle..*.*....... I46 Chapter IV. Discussion * 186 Chapter V. Summary............................. 233 PART II Studies on the pharmacology of petaline chloride, a convulsant alkaloid from Leontice leontopetalum Linn. Chapter I. Introduction ................ 235 Chapter II. A. Materials ......... 254 B. Experimental, 1. Convulsant-Anticonvulsant Activity (A) Comparison of the convulsive reactions and mortality induced by petaline chloride, leptazol and picrotoxin.............. ...255 - iv - .(B) Effect of pre-treatment with petaline chloride on the response to leptazol..... • •............... ..256 (C) Comparison of the effects of petaline chloride and phenobarbitone on electro-shock seizures,••••••••••• 257 2. Muscle Relaxant Activity (A) Cat gastrocnemius muscle-sciatic nerve preparation . • •....... 258 (B) Rat phrenic nerve-diaphragm preparation................. •. • • (i) Using Bell’s electrode......... .261 (ii) Using Collison's fluid electrode. 266 (C) Isolated frog rectus abdominis muscle preparation...... 270 3. Ganglion Blocking Activity Experiments on the nictitating membrane of the anaesthetised cat.... 271 4 . Experiments on Spinal Reflexes (A) Patellar tendon reflex............. 274 (B) Crossed extension reflex ......277 5. Cardiovascular Actions (A) Experiments on the blood pressure of the anaesthetised cat............... 278 (B) Experiments on the blood pressure of the spinal cat...... •••.•••••.......280 - v - (,C) Experiments on the blood pressure of the anaesthetised rat........... 280 (D) Experiments on the isolated perfused rat hindquarters ............... 283 (E) Experiments on the isolated perfused rabbit and kitten hearts........... 286 (E) Experiments on the isolated auricles of the guinea-pig............ 289 6. Effect on Smooth Muscle (A) Experiments on the isolated guinea-pig ileum................... •••••••••• 291 (B) Experiments on the isolated rat uterus......... 294 7. Toxic Effects on the Rabbit....... 296 Chapter III. Results - Convulsant-Anticonvulsant Activity (A) Comparison of the convulsive reactions and mortality induced by petaline chloride, leptazol and picrotoxin... 300 (B) Effect of pre-treatment with petaline chloride on the response to leptazol...... 300 (C) Comparison of the effects Of petaline chloride and phenobarbitone on electro—shock seizures....... 307 Muscle Relaxant Activity - vi - (A) Cat gastrocnemius muscle-sciatic nerve preparation................ (i) Neuromuscular blocking activity..** 307 (ii) Effect of indirect tetanization of the partially blocked muscle.... 313 (iii) Drug antagonism................. 316 (B) Rat phrenic nerve-diaphragm preparation..... *.............•*.. (i) Using Bell's electrode.......... 319 (ii) Using Collison's fluid electrode... 319 (C) Isolated frog rectus abdominis muscle preparation .... •••••• 323 Ganglion Blocking Activity Nictitating membrane of the anaesthetised cat........... 323 Experiments on Spinal Reflexes (A) Patellar tendon reflex........... 323 (C) Crossed extension reflex..... 328 Cardiovascular Action.............. (A) Blood pressure of the anaesthetised cat............................... 333 (B) Blood pressure of the spinal cat... 333 (C) Blood pressure of the anaesthetised rat....................... 333 (D) Isolated perfused rat hindquarters.•337 CE) Isolated perfused rabbit and kitten hearts. ....... 337 (F) Isolated guinea-pig auricles........337 Effects on Smooth Muscle (A) Isolated guinea-pig ileum........ * 342 (B) Isolated rat uterus............... 348 Toxic Effects on the Rabbit.......... 348 Chapter IV. Discussion.................... 357 Chapter V. Summary............................... 364 Appendix I. 366 Appendix II. 393 ti s viii - A 0 nO O E B & E M E N IS I have pleasure in recording my indebtedness to the many people who have helped me in-the work described in this thesis. I am grateful to Professor Stanley Alstead and Professor R.C. Garry of this University for their kindness in giving me the opportunity to carry out research in their laboratories. I wish to express
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