Methods in Drug Evaluation Prafulla Chandra Tiwari
INDEX
ABCDEFGHIKLMNOPRSTUVWXYZ
Page numbers followed by f refer to figure.
A
Acetazolamide 67
Acetylcholine
bioassay of 31
doses of 31
hydrochloride 88
Acetylsalicylic acid 89
Acid phosphatase 20
catalyzes 20
clinical significance 20
Acid secretion in perfused rat stomach 119
evaluation 120
procedure 119
Activated partial thromboplastin time 56, 57
Acute ischemia by injection of microspheres in dogs 53
evaluation 54
procedure 53
Adenosine triphosphate 11
Adrenaline 41
Akinesia 109
Alcuronium chloride 87
Alkaline phosphatase 11, 19, 23
clinical significance 19
types of 19
Allantoxanamide inhibits enzyme uricase 80
Allantoxanamide treatment in rats, hypouricemic activity after 80
Aminophylline 88
Anesthesia, endpoint of 114
Anesthetic
agents, local 115
dose, median 113
Anesthetized dog, method using 30
Angiotensin antagonism 45
Angiotensin converting enzyme 41, 44
inhibition in isolated guinea pig ileum 44
Anococcygeus muscle 42
contractions of 43
Antacids 119
Antagonistic activity 51, 52
Antianxiety agents 98
Antiasthmatic drugs 83
Anticoagulants 56
drugs 105
Antidiarrheal effect in cold-restrained rats, evaluation of 128
evaluation 128
procedure 128
Antidiarrheic agent 128
Antiepileptic drugs 105
Anti-goitrogenic activity 39
evaluation 40
procedure 39
Antiparkinsonian drugs 108
Antitoxin 25
Antitussive activity 92
after irritant inhalation in guinea pigs 92
evaluation 93
procedure 92
Antitussive agents 92
Antiuricosuric drugs 67
Anxiety 98
Anxiolytic drugs 98
Arachidonic acid 2
effect of 88
evaluation 89
procedure 88
Arrhythmia 9
Arterial bleeding time in mesentery 65
evaluation 66
procedure 65
Arteriovenous shunt thrombosis 64
evaluation 65
procedure 64
Aspartate transaminase and alanine transaminase 14
Astemizole 9
Atrium
left 44
right 43
Atropine sulfate 88
B
Benzodiazepine 100
receptor binding assay 102
evaluation 102
procedure 102
tissue preparation 102
Beta blocking effects in anesthetized dogs, screening for 51
Bezold-Jarisch reflex 50
evaluation 50
procedure 50
Bioassay 25
applications of 25
demerits of matching 27
of acetylcholine principle 31
of ach using rat ileum preparation 28f
of adrenaline 30
principle 30
standard preparation 30
of digitalis 32
of D-tubocurarine 32
procedure 32
rabbit head-drop method 32
of estrogen 35
of insulin 33
of noradrenaline 31
principle 31
procedure 31
of oxytocin 34
of oxytocin using rat uterus 34
evaluation 34
procedure 34
of thyroxine 38
principles of 26
procedure of
four point 29
three point 28
types of 26
Bleeding models 65
evaluation 65
procedure 65
Blind pharmacological screening 25
Blood coagulation tests 56
evaluation 57
procedure 56
Blood pressure
in conscious hypertensive rats 48
in pithed rats 47
evaluation 48
procedure 47
measurement 49
Blood sugar lowering effect in rabbits 33
procedure 33
Blood urea nitrogen 22
Body plethysmography and respiratory parameters 89
Bone
alkaline phosphatase level 12
diseases 20
Bradykinin potentiation 45
Bradykinin triacetate 88
Breathing air, normal 92
Bronchial perfusion of isolated lung 86
evaluation 86
procedure 86
Bronchodilating drug, effect of 89
Bronchospasmolytic activity in anesthetized guinea pigs 87
β-sympatholytic activity in isolated rat spleen 41
Bupivacaine 115
C
Calcium chloride 34
Cannula, implantation of 49
Carbachol 85
Carbamazepine 105
Carbonic anhydrase inhibition 67
evaluation 68
procedure 68
Carbonic anhydrase inhibitors 67
Cardiac arrest in guinea pigs, digitalis induced 26
Cardiac puncture technique 59
Cardiac toxicity, reports of severe 9
Cardiovascular drugs 41
Cardiovascular system 25
Carotid body denervation 91
Castor oil-induced diarrhea 127
evaluation 128
procedure 127
Cecocolic junction 126
Central nervous system 25, 94, 113, 125
diseases 17
stimulants and depressants 94
Chandler loop 58
evaluation 59
procedure 58
Charcoal Norit A 35
Cheng-Prusoff equation 104
Chicken blood pressure 34
evaluation 35
procedure 34
Chinchilla rabbits 45
Chloride secretion in rabbit colon, inhibition of 127
evaluation 127
procedure 127
Chronic gastric fistula 119
in rats 121
evaluation 121
procedure 121
Chronic renal failure
after subtotal nephrectomy in rats 76
in rats 75
evaluation 76
procedure 75
test 67
Clonazepam 102
Conduction anesthesia in sciatic nerve of frog 115
evaluation 116
procedure 115
Conduction anesthesia in sciatic nerve of rat 116
evaluation 116
procedure 116
Conduction anesthesia on mouse tail 116
evaluation 117
procedure 116
Congestive heart failure 41
Corneal reflex present 118
Coronary artery, left circumflex 53
Coronary thrombosis induced
by electrical stimulation 62
by stenosis 61
Cortical collecting duct 69
Cough induced by mechanical stimulation 93
evaluation 93
procedure 93
Creatine kinase 15, 16
Cromakalim 45
Cyclic flow reductions 61
Cyclooxygenase 2
enzyme 2
inhibitor of 89
Cytosol preparation 35
Cytosolic fraction binding 35
D
Dazoxiben HCl 89
Deep vein thrombosis 56
Dextran 35, 53
coated charcoal adsorption technique 35
Diarrhea-free period 128
Diarrheal excretion, early 128
Disodium hydrogen orthophosphate 34
Diuretic activity in rats 72
evaluation 73
procedure 72
Diuretic and saluretic activity in dogs 74
evaluation 74
procedure 74
Diuretics, clearance method of evaluation of 74
evaluation 75
procedure 74
Dopamine, prodrug of 111
Dose response curve 27
Dose studies
multiple ascending 8
single ascending 8
Drug 25
acting on lower urinary tract, evaluation of 80
acting on urinary tract 67
acting, screening of 25
affecting motility, evaluation of 94
classification of 24
development, stages 1
in process of 1
discovery 1
high throughput screening 2
latency, duration of 118
test 99
using isolated rat stomach, evaluation of 120
D-tubocurarine, test solution of 32
Duloxetine 67
E
Electric shock 107
Electrical-induced thrombosis 64
evaluation 64
procedure 64
Electroencephalogram threshold test in rats 113
evaluation 113
procedure 113
Electroshock in mice 107
evaluation 107
procedure 107
Elevated body swing test 111
evaluation 111
procedure 111
Endralazine 49
Enflurane 112
Enteric nervous system 125
Enteropooling test 126
evaluation 126
procedure 126
Enzymes 10, 11
in clinical practice 13
in diagnosis of diseases, application of 10
increased in serum in
cholestasis 23
liver damage 23
leak from cell 11
levels in serum and plasma, regulation of 11
production, alteration in 12
tests, selection of 12
Enzymology, clinical 10
Epilepsy 105
treatment of 105
Equivalent short circuit current 71
Estrogen receptor binding 35
procedure 35
Estrogen responsive element gene 37
Estrogens, transactivation assay for 37
evaluation 38
procedure 37
Ethosuximide 105
Etomidate 112
Ex vivo-assays 61
Eyelid closure 109
F
Fanconi's syndrome 20
Fecal pellet output 128
Fixed dose test 6
Flexed posture 109
Fluoroquinolone 9
Food effect 8
Functional plasma enzymes 10
G
GABAA receptor binding 100
evaluation 101
materials 100
procedure 100
GABA-mimetic agents 107
Gabapentin 105
Gama-amino butyric acid 100
Gamma-glutamyl transferase 23
Gastric acidity, measurement of 21
Gastric fluid, functional tests of 20
Gastric function tests 20
Gastric oxyntic glands 11
Gastrin, determination of activity of 122
evaluation 122
procedure 122
Gastrointestinal system, complex 125
Gastrointestinal tract 125
Gatifloxacin 9
General anesthetic 112
agents 112
Glomerular filtration rate 72
Glomerular function tests 22
Gould pressure transducer 91
Graphical bioassay 28
of acetylcholine employing rat ileum 28f
Guinea pig 43, 44
ileum 45
method 32
H
Halothane 112
Heart diseases 15, 16, 18
Helicobacter pylori 20
Hemodynamic measurements, preparation for 53
Histamine 85
dihydrochloride 84, 88
H3 receptor binding in brain 104
evaluation 104
procedure 104
receptor binding assay 83
evaluation 84
procedure 83
Histamine-induced bronchoconstriction 89
in anesthetized guinea pigs 89
Hole-board test 94, 95
procedure 95
Homogenates 35
Hormones 25
Human pharmacology 8
Hydroxy dopamine 110
Hypercholesterolemia 56
Hypertension 41
Hypoglycemic seizures in mice 33
evaluation 34
procedure 33
I
Imipramine-HCl 88
In vitro assay for GABAergic compounds 98
evaluation 100
procedure 98
In vitro methods 79
for evaluation of
antianxiety agents 98
diuretic and saluretic activity 67
In vitro tests 56, 83
In vivo methods 72
In vivo models 61
In vivo tests 87
Indomethacin-induced ulcers in rats 124
evaluation 124
procedure 124
Inhalation anesthetics, efficacy and safety of 114
evaluation 114
procedure 114
Inhalation toxicity, acute 7
Inhalational anesthetics 112
Inhibition of acid secretion 120
International Conference on Harmonization 4
Intracellular electrical measurements 71
Intracellular enzymes 12
Intravenous anesthetics, screening of 112
evaluation 113
procedure 112
Intravenous bolus injection 53
Intravenous injections of histamine 90
Intrinsic agonistic activity 51
Iodine release, inhibition of 39
evaluation 39
procedure 39
Isocitrate dehydrogenase of heart muscles 13
Isoenzymes 11, 18
and isoforms, measurement of 13
subunits 18
clinical significance 18
Isoflurane 112
Isoguvacine 99
Isolated blood vessels, contractile and relaxing activity on 45
Isolated kidney tubules, perfusion of 69
evaluation 70
procedure 69
Isolated perfused kidney method 72
evaluation 72
procedure 72
Isoniazid-induced convulsions 106
evaluation 107
procedure 106
Isonicotinic acid hydrazide 106
Isozymes 11
K
Kidney 25
diseases 19
Konzett-Rössler method 87
Krebs-Henseleit solution 85, 120
L
Lactate dehydrogenase 10, 17
enzyme 11
Late diarrheal excretion 128
Laxative activity in rats 125
evaluation 126
procedure 125
Laxative and antidiarrheal agents 125
Leukotriene 84, 88
LTC4 85
Levothyroxine 40
Lewy bodies 108
Lichtfield-Wilcoxon procedure 107
Lidocaine 116
Lipophilic character of drugs 5
Lipschitz test 72
Liver
cirrhosis 15
diseases 15, 18, 19
function tests 20, 22
L-triiodothyronine 40
Lysosomes 20
M
Magnesium chloride 34
Medullary collecting duct 69
Meissner's plexus 125
Membrane preparation 100
Methacholine 88
Microperfusion experiments 76
Micturition studies 80
evaluation 81
procedure 80
Milk ejection in lactating rabbit 35
evaluation 35
procedure 35
Mouse uterus cytosol, determination of specific binding in 36
Muscarinic agonists tremorine 108
Muscimol 99
Muscle coordination, tests for 96
grip strength 97
inclined plane 96
rotarod method 97
Muscle diseases 18
Myocardial infarction 13, 15, 56
after coronary ligation 52
evaluation 53
procedure 52
biomarker for 10
N
Nephrectomy, two-thirds 76
Nephritis, experimental 77
Nephrotoxic serum nephritis 77
evaluation 79
experimental protocol 78
procedure 78
Nephrotoxic serum, preparation of 78
Nerves, extrinsic 42
New drug application 8
New drug development process 1
Nicorandil 45
Nifedipine 49
Nuclear extract preparation 36
Nuclear uptake 36
O
Omperazole 119
Open field test 95
procedure 95
Ovalbumin 88
Oxaloacetate 14
Oxotremorine 108
antagonism 108
Oxygen consumption 38
evaluation 39
procedure 38
Oxygen-enriched air 47
Oxyhemoglobin 47
P
Paget's disease 20
Pancreas 11
Papillary collecting duct 69
Paracetamol 4
Parkinson's disease 108, 110
Patch clamp technique in kidney cells 68
evaluation 69
procedure 68
Pentobarbital 118
sodium 53, 88
Pentylenetetrazole test 105
Pentylenetetrazole-induced convulsions 105
evaluation 106
procedure 105
Perineal nerve 42
Peripheral venous catheter 125
Pharmacodynamics 4
Pharmacokinetics 3, 4
Pharmacological screening
and bioassay 24
types of 24
Photinus pyralis 37
Photocells 95
Picrotoxin 106
Picrotoxin-induced convulsions 106
evaluation 106
procedure 106
Pinacidil 45
Pirbright guinea-pigs 87
Pirbright white guinea pigs 90
Plasma
creatinine ratio 22
enzymes, non-functional 11
specific enzymes 10
Platelet aggregation 59, 60
substances 59
Platelet rich plasma, deaggregation in 59
Pneumotachography in anesthetized guinea pigs 90
Post-marketing surveillance 9
Postural tremor 109
Potassium channel openers, effects of 45
Potassium chloride 34
Preclinical studies 3
Procaine 116
Product characterization 3
Propofol 112
Prostaglandin synthesis inhibition 85
Prostaglandin treated animals 126
Prostate specific antigen 12
Prothrombin time 56, 57
Proton pump inhibitors 119
Psoas muscle 49
Pulmonary artery pressure 53
Pulmonary capillary pressure, mean 53
Pulmonary mechanics 91
Pulmonary resistance, calculation of 90
Pylorus ligation method 122
evaluation 123
procedure 122
R
Rabbit tooth pulp assay 117
evaluation 118
procedure 117
Rabbit's duodenum, method using 31
Rabeprazole 119
Rat anococcygeus muscle 42
isolated 42
Rat brain by telemetry, EEG analysis from 96
Renal function
evaluation of 74
impaired 75
tests 21
Renal pelvis, studies on 81
evaluation 82
procedure 81
Reserpine antagonism 110
evaluation 110
procedure 110
Respiratory depressant drugs
effects of 91
in conscious rats, effects of 91
Respiratory function in vivo 88
Retrobulbar block in dogs 118
evaluation 118
procedure 118
Rigidity 109
S
Salivary glands 11
Saluretic activity in rats 73
evaluation 73
procedure 73
Secreted enzymes 11
Serotonin receptor binding assay 103
evaluation 104
procedure 103
tissue preparation 103
Serum
albumin 22
bilirubin 22
creatine kinase 16
enzymes 22
Sevoflurane 112
Simple pharmacological screening 25
Skeletal muscle disease 15, 17
Sodium chloride 34
Sodium cyanide 91
Sodium dihydrogen orthophosphate 34
Sodium hydrogen carbonates 34
Spasmolytic activity in isolated
guinea pig lung strips 84
trachea 85
evaluation 85
procedure 85
Sprague-Dawley or Wistar rats, female 34
Sprague-Dawley rats 41, 120
adult 113
male 39, 47, 50, 91
Stress ulcer through immobilization stress 123
evaluation 123
procedure 123
Strychnine-induced convulsions 106
evaluation 106
procedure 106
Subaqueous tail bleeding time in rodents 65
Subcritical stenosis 61
Succinylcholine 89
Sucrose 99
Synthetic function, tests for 23
Systolic blood pressure 48
T
Tail cuff method 48
Tensile strength of connective tissue in rats 40
Test tube to new drug application, steps from 2f
Thiazides 67
Thrombin time 56
Thromboelastography 57
alpha angle 58
clot
formation time 58
strength 58
evaluation 58
procedure 57
reaction time 58
Thromboxane synthetase, inhibitor of 89
Thyroid
diseases 17
enlargement 39
hormones, modified for 40
Tiagabine 105
Tissue preparation 99
Tolpropamine-HCl 88
Toxic class method, acute 6
Toxicological studies 6
Toxins 25
Transepithelial electrical measurements 71
Transpulmonary pressure 90
Tremorine 108
Tris-sucrose buffer 35
Tubular function tests 22
Tumor lysis syndrome, acute 67
Tumors 19
Tyrode's solution 44
U
Urapidil 49
Uricosuric and hypouricemic activity 79
Urinary bladder and internal urethral sphincter 82
Urinary incontinence, management of 67
V
Vaginal cornification 38
evaluation 38
procedure 38
Valproic acid 105
Vigabatrin 105
Vitamins 25
Volatile anesthetics, screening of 113
evaluation 114
procedure 113
Volatile anesthetics, testing of 113
W
Washed platelets (born method) 59
Wilson's disease 23
Wistar rats, male 72
X
Xanthine oxidase catalyzes 79
Y
Yohimbine-induced convulsions 107
evaluation 107
procedure 107
Z
Zollinger-Ellison syndrome 21
×
Chapter Notes

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fm1Methods in Drug Evaluation
fm2fm3Methods in Drug Evaluation
Prafulla Chandra Tiwari M Pharm (Pharmacology) Senior Research Fellow Department of Pharmacology and Therapeutics King George's Medical University Lucknow, Uttar Pradesh, India Foreword Durga Nand Tripathi
fm4
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Methods in Drug Evaluation
First Edition: 2018
9789352701469
Printed at
fm5Dedicated to
My Mother Pratibha Tiwari,
Father Pravesh Chandra Tiwari,
Sister Priyanka Tiwari
and
Wife Preeti Tiwari.fm6
fm7Foreword
I am delighted to see this book of experimental Pharmacology written by my student Mr Prafulla Chandra Tiwari. I remember my graduation days when we have very limited option of experimental pharmacology books. I am very happy to see that Prafulla make a huge contribution to fulfill that gap by writing this book. Let me describe first about the Prafulla that how we know each other. I taught Prafulla Pharmacology during his graduation at Faculty of Pharmacy, Babu Banarasi Das National Institute of Technology and Management (BBDNITM), Lucknow and he impressed me a lot with his inquisitive nature and intelligence. Slowly, Prafulla build a wonderful relationship with me by his sincerity, devotion and knowledge in the subject and strong desire to pursue a career in the field of Pharmacology, and I strongly believe this book is the creation of that desire. He is one of the brightest students of mine; I have proud of him and delighted to write few lines about his book.
After reading this book I found this is an outstanding creation and will be helpful to the readers in designing the experiment, execution, analysis of results and making concept and deep understanding in the subjects. This book wonderfully describe about the drug development process, experimental setup for screening of the compound having activity on cardiovascular system, central nervous system, GI system as well as blood and urinary tract system. This book is extremely useful for students learning the experiment of Pharmacology during their graduation and postgraduation as well as work as reference in industry.
Durga Nand Tripathi PhD
Instructor
Mol & Cell Biology-Walker
Baylor College of Medicine
Houston, TX 77030, USAfm8
fm9Preface
This book is about the scientific methods and thinking that “Pharmacologists” use for new drug discovery. By understanding and applying these methods, students can develop new animal models for drug discovery process. In addition, you will be able to make suggestions to others and even detect flaws in research. Some of these flaws are common in popular thinking. This book has a number of features that are designed to help you accomplish your goals for this course. The first on our list is perhaps the most important.
Prafulla Chandra Tiwarifm10
fm11Acknowledgments
This book itself is an acknowledgment to the intensity drive and technical competence of many individuals who have contributed to it. I feel proud to list here few of them. I am very much indebted to Dr Rishi Pal and Dr Durga Nand Tripathi, who are my mentors and constant source of inspiration.
Sincerely I express my deep feelings to my friends specially Dharmendra Kumar Singh, Mayank Jain and Shipra Kartik who rendered a helping hand in the hour of need.
I am indebted to my Father Pravesh Chandra Tiwari, mother Pratibha Tiwari, sister Priyanka Tiwari and wife Preeti Tiwari for their moral support and personal sacrifice to see me through this book project.