Enhancement of noradrenergic neural transmission: an effective therapy of myasthenia gravis: a report on 52 consecutive patients.
Neurochemical, neuroautonomic and neuropharmacological assessments carried out on all our myasthenia gravis (MG) patients showed that they presented a neural sympathetic deficit plus excessive adrenal-sympathetic activity. These abnormalities were registered during the basal (supine-resting) state, as well as after several stress tests (orthostasis, exercise, oral glucose and buspirone). In addition, MG patients showed increased levels of free-serotonin (f5HT) in the plasma, supposedly associated with the increased platelet aggregability which we found in all MG patients. As the above trio of neurochemical disorders (low noradrenergic-activity + high adrenergic-activity + increased f-5HT plasma levels) is known to favor Th-1 immunosuppression + Th-2 predominance, we outlined a neuropharmacological strategy for reverting the above neurochemical disorder. This treatment provoked sudden (acute), and late sustained improvements. Acute effects have been attributed to the increase of alpha-1 activity at the spinal motoneuron level. Late improvements always paralleled a significant normalization of immunological disorders. Complete normalization was registered only in non-thymectomized MG patients.
Lechin
F
F
Section of Neuropharmacology, Instituto de Medicina Experimental, Universidad Central de Venezuela. flechin@telcel.net.ve
van der Dijs
B
B
Pardey-Maldonado
B
B
John
E
E
Jimenez
V
V
Orozco
B
B
Baez
S
S
Lechin
M E
ME
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use; D002065:Buspirone / Q000627:therapeutic use; D003891:Desipramine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004576:Electromyography; D004837:Epinephrine / Q000097:blood*; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018377:Neurotransmitter Agents / Q000627:therapeutic use*; D009638:Norepinephrine / Q000097:blood*; D010649:Phenylalanine / Q000627:therapeutic use; D010974:Platelet Aggregation; D011433:Propranolol / Q000627:therapeutic use; D012701:Serotonin / Q000097:blood; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014443:Tyrosine / Q000627:therapeutic use
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D001559:Benzhydryl Compounds; D006877:Hydroxamic Acids; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D014443:Tyrosine; D010649:Phenylalanine; D011433:Propranolol; C022116:adrafinil; D000077408:Modafinil; D003891:Desipramine; D002065:Buspirone; D009638:Norepinephrine; D004837:Epinephrine