Dopaminergic Ergot Derivatives and Motor Function (eBook)

Front Cover 1
Dopaminergic Ergot Derivatives and Motor Function 4
Copyright Page 5
Table of Contents 6
LIST OF PARTICIPANTS 10
PREFACE 14
SECTION I: DOPAMINERGIC MECHANISMS 16
CHAPTER 1. THE ANATOMY OF THE EXTRAPYRAMIDAL SYSTEM 18
INTRODUCTION 18
STRIATUM 18
GLOBUS PALLIDUS 24
SUBTHALAMIC NUCLEUS 27
SUBSTANTIA NIGRA 28
COMMENT 30
ACKNOWLEDGEMENTS 31
REFERENCES 32
CHAPTER 2. CHEMICAL ASPECTS OF ERGOT DERIVATIVES WITH CENTRAL DOPAMINERGIC ACTIVITY 38
ABSTRACT 38
INTRODUCTION 38
ERGOPEPTINES, ERGOLINES, CLAVINES 38
STRUCTURE-ACTIVITY RELATIONSHIP 43
REFERENCES 46
CHAPTER 3. BIOCHEMICAL ANATOMY OF THE EXTRAPYRAMIDAL SYSTEM 48
NEUROANATOMY OF THE EXTRAPYRAMIDAL SYSTEM 48
THE STRIATUM AND PALLIDUM 49
THE SUBSTANTIA NIGRA 52
INTERACTIONS AMONG VARIOUS POPULATIONS OF NEURONS 53
CONCLUDING REMARKS 53
REFERENCES 54
CHAPTER 4. PATHOPHYSIOLOGY OF MOTOR PERFORMANCE IN PARKINSON'S DISEASE 60
INTRODUCTION 60
STUDIES OF REACTION TIME AND SPEED OF MOVEMENT 60
RESPONSES TO LIMB DISPLACEMENT IN PD 65
MECHANISMS UNDERLYING TREMOR 68
MECHANISMS UNDERLYING POVERTY OF MOVEMENT 70
ACKNOWLEDGEMENT 71
REFERENCES 72
CHAPTER 5. DOPAMINERGIC ERGOTS: DRUGS WHICH DISCRIMINATE BETWEEN THE MULTIPLE CLASSES OF DOPAMINE RECEPTORS 76
INTRODUCTION 76
BIOCHEMICAL SPECIFICITY OF DOPAMINERGIC ERGOTS 79
SUMMARY AND CONCLUSIONS 83
REFERENCES 84
CHAPTER 6. DOPAMINE RECEPTORS AND PHOSPHODIESTERASES 88
Relationship between dopamine receptors and phosphodiesterases 88
Effect of phosphodiesterase inhibitors on dopaminergic mechanisms 90
Effect of phosphodiesterase inhibitors on rotation behaviour 91
Interaction of the phosphodiesterase inhibitors with adenosine 92
References 95
CHAPTER 7. SPECIFICITY OF AGONISTS AND ANTAGONISTS AT MODEL RECEPTORS FOR DOPAMINE AND OCTOPAMINE 100
ABSTRACT 100
INTRODUCTION 101
RESULTS 101
REFERENCES 113
CHAPTER 8. INFLUENCE OF ERGOT DERIVATIVES ON THE DIFFERENT TYPES OF DOPAMINE RECEPTORS AND ON OTHER AMINE RECEPTORS IN PRIMATE BRAIN 116
ABSTRACT 116
INTRODUCTION 117
METHODS 117
RESULTS 117
CONCLUSIONS 126
REFERENCES 127
CHAPTER 9. DOP AMINE AND HUNTINGTON'S DISEASE: ASSESSMENT USING THE KAINIC ACID MODEL 130
METHODS 130
RESULTS 132
DISCUSSION 135
SUMMARY 139
ACKNOWLEDGEMENTS 140
REFERENCES 140
SECTION II: DOPAMINERGIC AGONISM OF ERGOT DERIVATIVES 142
CHAPTER 10. NEUROPHARMACOLOGY OF ERGOT DERIVATIVES 144
ABSTRACT 144
INTRODUCTION 144
BIOCHEMICAL STUDIES 145
FUNCTIONAL STUDIES 147
REFERENCES 153
CHAPTER 11. ACTIONS OF ERGOT DERIVATIVES AT DOPAMINE SYNAPSES 156
EFFECTS OF ERGOT DRUGS ON 3H-SPIROPERIDOL BINDING IN STRIATUM OF EXPERIMENTAL RATS 158
EFFECTS OF ERGOT DRUGS ON ADENYLATE CYCLASE ACTIVITY 160
BEHAVIOURAL ACTIONS OF DOPAMINERGIC ERGOT DERIVATIVES 164
COMPARISONS BETWEEN THE EFFECTS OF DIFFERENT TYPES OF D0PAMINERGIC ERGOT DERIVATIVES ON CENTRAL D0PAMINERGIC MECHANISMS 165
EFFECTS OF ERGOT DRUGS ON LIMBIC DA RECEPTORS AND CENTRAL 5-HT RECEPTORS 167
EFFECTS OF ERGOT DRUGS ON CENTRAL a-ADRENERGIC RECEPTORS 168
ACKNOWLEDGEMENTS 169
REFERENCES 171
CHAPTER 12. DOPAMINERGIC ERGOT DERIVATIVES: SELECTIVE AGONISTS OF A NEW CLASS OF DOPAMINE RECEPTORS? 174
EFFECTS ON CELL-EKEE PREPARATIONS 175
EFFECTS ON SLICES OF NEOSTIATUM 178
EFFECTS ON IN VIVO PRODUCTION OF STRIATAL CYCLIC AMP AND CEREBELLAR CYCLIC GMP 180
DISCUSSION AND CONCLUSIONS 182
REFERENCES 184
CHAPTER 13. ACTION OF ERGOT DOPAMINERGIC AGONISTS ON MONOAMINE SYNTHESIS IN RAT BRAIN 188
CATECHOLAMINE SYNTHESIS IN RAT BRAIN 188
5-HT SYNTHESIS 192
CATECHOLAMINE AND 5-HT SYNTHESIS AFTER PRETREATMENT WITH RESERPINE 193
ACTION OF ERGOT DERIVATIVES AT PRESYNAPTIC D0PAMINE RECEPTORS 195
CONCLUSIONS 198
REFERENCES 199
CHAPTER 14. BEHAVIOURAL EFFECTS OF ERGOT DRUGS 202
ABSTRACT 202
INTRODUCTION 202
METHODS 203
RESULTS 206
DISCUSSION 215
REFERENCES 218
CHAPTER 15. EFFECTS OF ERGOLINES ON DOPAMINERGIC AND SEROTONERGIC SINGLE UNIT ACTIVITY 222
INTRODUCTION 222
EFFECTS OF LISURIDE AND LERGOTRILE ON DOPAMINERGIC UNIT ACTIVITY 223
EFFECTS ON SEROTONERGIC UNIT ACTIVITY 231
CORRELATIONS WITH BEHAVIORAL, BIOCHEMICAL, AND CLINICAL OBSERVATIONS 232
ACKNOWLEDGEMENT 234
REFERENCES 234
CHAPTER 16. DOPAMINERGIC AND SEROTONERGIC EFFECTS OF ERGOT DRUGS 238
INTRODUCTION 238
METHODS 239
RESULTS 240
DISCUSSION 247
REFERENCES 249
CHAPTER 17. PHARMACOLOGICAL EFFECTS OF LISURIDE IN RODENTS MEDIATED BY DOPAMINERGIC RECEPTORS: MECHANISM OF ACTION AND INFLUENCE OF CHRONIC TREATMENT WITH LISURIDE 252
MATERIAL AND METHODS 254
RESULTS 256
DISCUSSION 263
Bibliography 264
CHAPTER 18. THE DOPAMINEPHILLIC PROPERTIES OF ERGOLINE DERIVATIVES 268
INTRODUCTION 268
DISCUSSION 272
SUMMARY 274
REFERENCES 274
SECTION III: THERAPEUTIC ACTIONS OF ERGOT DERIVATIVES 276
CHAPTER 19. CLINICAL PHARMACOLOGY OF ERGOTS 278
CHAPTER 20. ACTIONS OF BROMOCRIPTINE IN THE SHY-DRAGER AND STEELE - RICHARDSON - OLSZEWSKI SYNDROMES 286
INTRODUCTION 286
METHODS 286
RESULTS 288
DISCUSSION 294
CONCLUSION 296
ACKNOWLEDGEMENT 296
REFERENCES 296
CHAPTER 21. MODIFICATION OF THE "ON-OFF" EFFECT WITH BROMOCRIPTINE AND LERGOTRILE 300
ABSTRACT 300
INTRODUCTION 300
METHODS 300
RESULTS 301
DISCUSSION 302
ACKNOWLEDGEMENT 303
REFERENCES 309
CHAPTER 22. BROMOCRIPTINE COMPARED WITH LEVODOPA IN PARKINSONISM 312
REFERENCES 316
CHAPTER 23. ROLE OF BROMOCRIPTINE IN THE TREATMENT OF PARKINSONISM 318
ABSTRACT 318
INTRODUCTION 318
METHODS 318
RESULTS 321
DISCUSSION 325
ACKNOWLEDGEMENTS 326
REFERENCES 326
CHAPTER 24. DOSE-DEPENDENT LOCOMOTOR EFFECTS OF BROMOCRIPTINE IN ANIMALS AND MAN —ARE SOME OF ITS ACTIONS DUE TO METABOLITES? 328
ABSTRACT 328
INTRODUCTION 328
LOCOMOTOR EFFECTS IN ANIMALS 328
LOCOMOTOR EFFECTS IN MAN 329
PRE- AND POST-SYNAPTIC ACTIONS OF BROMOCRIPTINE 330
ARE BROMOCRIPTINE'S ACTIONS ON DOPAMINE RECEPTORS DUE TO METABOLITES? 331
ACKNOWLEDGEMENTS 332
REFERENCES 332
CHAPTER 25. RELATIONSHIP BETWEEN BRAIN DOPAMINE TURNOVER AND THE THERAPEUTIC RESPONSE TO BROMOCRIPTINE 334
ABSTRACT 334
INTRODUCTION 334
PATIENTS AND METHODS 334
RESULTS 335
DISCUSSION 337
ACKNOWLEDGEMENT 338
REFERENCES 338
CHAPTER 26. BROMOCRIPTINE AS AN ADJUVANT TO LEVODOPA 344
ABSTRACT 344
INTRODUCTION 344
METHODS 344
RESULTS 345
BENEFICIAL EFFECTS 345
SIDE EFFECTS 347
DISCUSSION 348
REFERENCES 349
CHAPTER 27. ERGOT DERIVATIVES WITHOUT LEVODOPA IN PARKINSONISM 352
ABSTRACT 352
INTRODUCTION 352
PATIENTS AND METHODS 352
RESULTS 353
DISCUSSION 353
REFERENCES 354
CHAPTER 28. CLINICAL OBSERVATIONS WITH BROMOCRIPTINE IN PARKINSONISM 358
INTRODUCTION 358
DOUBLE-ELIND CROSS-OVER TRIAL 358
BROMOCRIPTINE WITH OR WITHOUT LEVODOPA 359
PLASMA CONCENTRATION OF BROMOCRIPTINE 361
CONCLUSIONS 361
ACKNOWLEDGEMENT 361
REFERENCES 361
CHAPTER 29. ERGOT DERIVATIVES IN THE TREATMENT OF PSYCHOTIC AND HYPERKINETIC DISORDERS 364
INTRODUCTION 364
APOMORPHINE 365
ERGOT DERIVATIVES 367
CF 25-397 370
CONCLUSIONS 370
REFERENCES 372
CHAPTER 30. ERGOT DERIVATIVES IN DYSKINETIC AND DYSTONIC DISORDERS 376
SUMMARY 376
INTRODUCTION 376
PATIENTS AND METHODS 377
CLINICAL RESULTS 379
DISCUSSION 381
REFERENCES 382
SECTION IV: ADVERSE REACTIONS OF ERGOT DERIVATIVES 386
CHAPTER 31. TOXICITY OF ERGOT ALKALOIDS 388
INTRODUCTION 388
TYPES OF ERGOT TOXICITY 388
RELATION OF TOXIC EFFECTS TO KNOWN PHARMACODYNAMIC ACTIONS 390
ANIMAL TOXICITY STUDIES 392
BROMOCRIPTINE TOXICITY 393
CONCLUSIONS 394
REFERENCES 394
CHAPTER 32. CARDIOVASCULAR EFFECTS OF ERGOT DERIVATIVES IN MAN 396
INTRODUCTION 396
BLOOD PRESSURE AND HEART RATE 396
EFFECTS ON THE PERIPHERAL CIRCULATION 397
INTERACTIONS WITH BIOGENIC AMINES 404
REFERENCES 405
CHAPTER 33. CARDIOVASCULAR REACTIONS TO BROMOCRIPTINE 410
ABSTRACT 410
INTRODUCTION 410
CONCLUSIONS 416
ACKNOWLEDGEMENTS 416
REFERENCES 416
CHAPTER 34. PSYCHIATRIC REACTION TO ERGOT DERIVATIVES 420
REFERENCES 427
CHAPTER 35. THE HEPATOTOXICITY OF ERGOT ALKALOIDS 430
ABSTRACT 430
INTRODUCTION 430
METHODS 431
RESULTS 431
DISCUSSION 439
ACKNOWLEDGEMENTS 440
REFERENCES 442
CHAPTER 36. ENDOCRINE EFFECTS OF DOPAMINERGIC ERGOT ALKALOIDS —TOXICOLOGICAL IMPLICATIONS 446
ABSTRACT 446
INTRODUCTION 446
ANTERIOR PITUITARY HORMONE SECRETION AND EFFECTS OF DOPAMINE AGONISTS 446
COMPARISON OF THE MENSTRUAL CYCLE AND ESTRUS CYCLE OF THE RAT 449
INVOLUTION OF REPRODUCTIVE FUNCTION IN WOMEN AND FEMALE RATS 450
THE EFFECTS OF BROMOCRIPTINE ON REPRODUCTIVE FUNCTION IN THE FEMALE 451
THE ENDOMETRIAL STUDIES IN WOMEN 451
DISCUSSION 453
REFERENCES 454
SUBJECT INDEX 458