Screening Methods in Pharmacology (eBook)

Front Cover 1
Screening Methods in Pharmacology 4
Copyright Page 5
Table of Contents 10
Dedication 6
PREFACE 8
Chapter 1. INTRODUCTION 18
Chapter 2. A BRIEF REVIEW OF THE BIOCHEMISTRY OF THE NERVOUS SYSTEM 20
I. Chemical Mediators 20
II. Some Mechanisms of Drug Effects Within the Autonomic System 24
III. Mechanisms Within the Parasympathetic System 25
IV. Mechanisms Within the Sympathetic System 28
Chapter 3. THE ORGANIZATION OF SCREENING 39
I. Introduction 39
II. Further Remarks on Blind Screening 41
III. Neuropharmacological Tests in Blind Screening 43
IV. An Alternative Schedule 51
V. Tests Other than Neuropharmacological 53
VI. Tests Subsequent to Those in Blind Screening 57
Chapter 4. GENERAL METHODS 59
I. Introduction 59
II. Tests on Isolated Organs 59
III. The Guinea Pig Ileum 60
IV. The Vas Deferens of the Guinea Pig 64
V. The Jejunum of the Rat 66
VI. The Seminal Vesicle of the Rat 66
VII. Seminal Vesicle of the Guinea Pig 67
VIII. Fundus Strip of the Rat 68
IX. The Duodenum of the Rat 70
X. Other Isolated Organs 70
XI. Cardiovascular Tests (Electrical and Chemical) 72
XII. Food Consumption 75
Chapter 5. QUANTAL RESPONSES. CALCULATION OF THE ED 77
I. Introduction 77
II. Graphical Calculation of Miller and Tainter 78
III. Arithmetical Method of Reed and Muench 79
IV. Arithmetical Method of Kärber 80
V. The pA Scale 81
VI. Tests with Superfusion Drug Antagonism
VII. The Graphical Method of Litchfield and Wilcoxon 84
Chapter 6. DEPRESSANTS OF THE CENTRAL NERVOUS SYSTEM 86
I. Introduction 86
II. The Righting Reflex 86
III. Antagonism to Various Chemical Stimulants 87
IV. Palpebral Test 91
V. Runway Test for Thirsty Rats 91
VI. Motor Deficit 92
VII. Motor Control on an Inclined Plane 92
VIII. Natatory Exhaustion 93
IX. Amphetamine Antagonism 94
X. Motor Activity 95
XI. Cornea and Pinna Reflexes 95
XII. Pentylenetetrazol (Metrazol) Antagonism 96
XIII. A Test Group for Central Depressants 97
XIV. Central Anesthetics 99
Chapter 7. ATARACTIC (TRANQUILLIZING, NEUROLEPTIC) AGENTS 104
I. Introduction 104
II. Behavioral Test Group 105
III. Ratio of Reflexes in the Mouse 109
IV. Avoidance of Electrical Shock. A Test of Suppression of a Conditioned Response 111
V. Suppression of Combativeness 111
VI. Head-Withdrawal Reflex 115
VII. Yohimbine Syndrome 115
VIII. Open Field Test 116
IX. Conclusion 116
Chapter 8. ANALGESICS 117
I. Introduction 117
II. Narcotic Analgesics 118
III. Nonnarcotic Analgesics 130
Chapter 9. OXYTOCIC AGENTS 135
I. Introduction 135
II. Qualitative Test for Uterine Stimulation 135
III. Quantitative Procedure 136
IV. Tests Performed on the Uterus in situ 142
Chapter 10. ANTISEROTONIN AGENTS 144
I. The Isolated Uterus of the Rat 144
II. Isolated Uterus Bathed in Antagonist 145
III. Uterus Bathed in Antagonist. Alternative Method 146
IV. Antiedema Test on the Foot of the Rat 147
V. Cardiovascular Test on the Dog Given Chlorisondamine 148
VI. Antagonism to Serotonin-Induced Convulsions 148
VII. Ileum of the Guinea Pig D Receptors
VIII. Pyretogenic Effects 150
Chapter 11. PARASYMPATHOLYTIC AGENTS 152
I. Mydriasis 152
II. Antisialagogue Activity 154
III. Prevention of Intestinal Spasm 156
IV. Lacrimation 157
V. Tests in vitro 157
VI. Gastrointestinal Propulsion 159
Chapter 12. SYMPATHOLYTIC AGENTS 160
I. Introduction 160
II. Epinephrine Antagonism 160
III. Prolapse of the Nictitating Membrane 162
IV. Blood Pressure of the Rat The ADC
V. Splenic Strip of the Cat 163
VI. The Two Kinds of Receptor 165
VII. The Perfused Rabbit Ear 167
Chapter 13. ANTI-INFLAMMATORY AGENTS 169
I. Introduction 169
II. Pedal Inflammation Induced by Chemical Agents 169
III. Implantation of a Pellet 175
IV. Granuloma Pouch 175
V. Erythema 177
VI. Tuberculin Sensitivity 177
VII. Inhibition of Ascites 178
VIII. Hyaluronidase Inhibition 178
IX. Pleural Fluid 179
X. Freund's Adjuvant 179
Chapter 14. ANTICONVULSANTS 181
I. Introduction 181
II. Convulsions Induced by Chemicals 181
III. Convulsions Induced by Electroshock 183
IV. Combined Procedures 183
V. Tryptamine Potentiation and Antagonism 185
VI. Tremorine 186
VII. The Rapid Screening for Myorelaxant Agents 188
Chapter 15. SYMPATHOMIMETIC AGENTS 190
I. Introduction 190
II. Mydriasis 191
III. The Uterus and Ascending Colon of the Rat 192
IV. The Rectal Cecum of the Hen 193
V. The Isolated Spleen of the Cat 193
Chapter 16. CENTRAL STIMULANTS 195
I. Introduction 195
II. Analeptic Agents 196
III. "Sandauswurf" (Displacement of Sand) 196
IV. Registration of Motor Activity 198
V. Runway Test 198
VI. Ptosis Test 199
VII. "Zwangsnagen" Induced by Apomorphine 199
VIII. Intracerebral Test 201
IX. Ingestion of Food Anoretic and Central Stimulant Activity
X. Duration of Anesthesia Respiratory Analeptics
Chapter 17. MUSCARING AGENTS 207
I. The Isolated Eye of Rodents 207
II. The Isolated Trachea of the Rat 208
Chapter 18. GANGLION-BLOCKING AGENTS 210
I. Introduction 210
II. Antagonism of Nicotine 211
III. The Inferior Eyelid of the Rat 212
IV. The Blood Pressure of the Upright Rabbit 213
Chapter 19. ANTIFIBRILLATORY AGENTS 214
I. Introduction 214
II. Arrhythmia Induced by Acetylcholine and Potassium Deficiency 215
III. Arrhythmia Induced by Aconitine 216
IV. Arrhythmia Induced by Maximum Frequency 217
V. Ventricular Arrhythmia induced by Calcium 219
Chapter 20. CARDIOTONIC AGENTS 220
I. The Papillary Muscle of the Cat 220
II. The Atrium of the Cat and the Rat 222
III. The Aortic Strip of the Rabbit 224
Chapter 21. HISTAMINE-LIKE AGENTS 227
I. Perfusion of the Hind Quarters and the Lung 227
II. Perfusion of the Skin 228
Chapter 22. ANTIHISTAMINE AGENTS 230
I. Introduction 230
II. Intravenous Toxicity 231
III. Histamine Aerosol 231
IV. Direct Antagonism to Histamine 233
V. Anaphylactic Microshock 234
VI. Other Methods 234
Chapter 23. ANTITUSSIVE AGENTS 235
I. Cough Induced by Ammonia in the Cat 235
II. Cough Induced by Citric Acid in the Guinea Pig 236
III. Cough Induced by Sulfuric Acid in the Dog 237
Chapter 24. ANTACID AGENTS 238
I. Ulceration and Acidity in the Shay Rat 238
II. Gastric Perfusion in the Rat 239
III. The Isolated Heal Segment 241
Chapter 25. THYROMIMETIC AGENTS 242
Chapter 26. HYPOGLYCEMIC AGENTS 244
Chapter 27. CHOLERETIC AGENTS 246
Chapter 28. ANTIPARKINSON AGENTS 248
Chapter 29. ANTI-INFLAMMATORY AND GLUCOCORTICOIDAL AGENTS 250
Chapter 30. ANTIEMETIC AGENTS 252
Chapter 31. BRONCHODILATANT AGENTS 255
Chapter 32. CURARIFORM AGENTS 257
I. Paralysis of Intact Animals 257
II. The Phrenic Nerve and Diaphragm of the Rat 258
III. The Biventer Cervicis of the Chicken 259
Chapter 33. ANABOLIC, ANDROGENIC, AND ANTIANDROGENIC AGENTS 261
Chapter 34. POTENTIATORS AND ANTAGONISTS OF TRYPTAMINE 264
Chapter 35. VASOPRESSIVE PEPTIDES 266
Chapter 36. DIURETIC AND NATRIURETIC AGENTS 268
Chapter 37. ANTICHOLINESTEHASE AGENTS 272
Chapter 38. ANTICHOLESTEROL AGENTS 276
Chapter 39. URICOSURIC AGENTS 279
Chapter 40. ANTISHOCK AGENTS 281
Chapter 41. HEMOSTATIC AGENTS 283
Chapter 42. LOCAL AND SPINAL ANESTHETICS 285
Chapter 43. ABORTIFACIENT AGENTS 287
Chapter 44. THYMOLEPTIC AGENTS 290
I. Introduction 290
II. Qualitative Screening Methods 290
III. Amine Depletion in the Central Nervous System 292
IV. Inhibition of Monoamine Oxidase 293
V. Rats Having Septal Lesions 295
Chapter 45. DERMAL IRRITANTS 296
Chapter 46. TERATOGENIC AGENTS 299
APPENDIX 301
I. A Summary of Often Used Formulas in Statistics 301
II. An Approximate Formula for Statistical Significance 303
III. Statistical Analysis of Responses in Groups of Animals: Salivation in Rabbits 304
IV. Four-Point Assay of Substances Causing Tachyphylaxis 308
V. Right-Left Assay 310
VI. The Composition of Solutions Used for the Bathing of Tissues 314
VII. Formulas for Use in the Injection of Animals 314
VIII. An Antipyretic Test 315
IX. A Test for Dermal Absorption 316
X. Tests for Hepatotoxicity 316
XI. Serum Cholesterol 317
XII. Anesthetics for Laboratory Animals 318
XIII. Acute Toxicity: The Determination of the LD50 319
XIV. A Test for the Normal Distribution of a Set of Numbers 321
REFERENCES 322
AUTHOR INDEX 332
SUBJECT INDEX 339