ABSTRACT
Serum or IgM fraction from two patients with a demyelinating neuropathy and IgM monoclonal antibodies to myelin-associated glycoprotein were injected in three different animal species. There were no clinical, electrophysiological or morphological signs of demyelination in either chronic or acute passive transfer experiments. These results suggest that the pathogenesis of this human demyelinating neuropathy may be more complex than has been assumed.
Subject(s)
Demyelinating Diseases/immunology , Immunization, Passive , Myelin Proteins/immunology , Peripheral Nervous System Diseases/immunology , Animals , Animals, Newborn , Antibodies, Monoclonal , Callithrix , Demyelinating Diseases/etiology , Guinea Pigs , Humans , Immunoglobulin M , Myelin-Associated Glycoprotein , Peripheral Nervous System Diseases/etiology , RabbitsABSTRACT
Desipramine (DMI), like many antidepressant drugs, inhibit the production of paradoxical sleep (PS). In the present experiment, we have investigated the relationships between brain level of DMI and PS inhibition. Groups of rats had their sleep monitored after 1, 2 or 4 mg/kg of DMI. In other animals, the brain concentration of DMI was assayed at various times after the same treatments. The results indicate that a critical threshold concentration of 300 ng/g DMI in the brain is necessary for complete PS inhibition. This stage reappears only when the DMI level falls below this value, and its production resumes at a normal rate, provided the DMI level reached initially was not largely in excess of the threshold concentration. The results are discussed with regard to the present knowledge of specific binding of tricyclics in brain and their "ex vivo" action on norepinephrine uptake resulting in enhancement of collateral inhibiton of noradrenergic cells.
Subject(s)
Brain/metabolism , Desipramine/metabolism , Sleep, REM/drug effects , Animals , Brain/drug effects , Brain Stem/metabolism , Cerebral Cortex/metabolism , Desipramine/pharmacology , Dose-Response Relationship, Drug , Hippocampus/metabolism , Male , Rats , Rats, Inbred Strains , Reaction Time/drug effectsABSTRACT
In order to reinvestigate the role of brain alpha-adrenergic systems in the regulation of paradoxical sleep (PS), we recorded chronically implanted rats under the effect of various neuroactive substances. The functions describing the evolution of PS during sleep were calculated. The following substances were studied at different doses, alone and in various combinations: clonidine, phenoxybenzamine, chlorpromazine, yohimbine, piperoxane and desipramine. Chlorpromazine, yohimbine, piperoxane and desipramine were also studied after pretreatment with alpha-methylparatyrosine. The results are discussed in terms of the known pharmacological properties of these compounds, and indicate that brain alpha-adrenergic systems, probably mainly noradrenergic systems, are positively involved in the maintenance of PS. However, the activity of these systems is controlled by powerful regulatory mechanisms: inhibitory control of transmitter release at the effector site, collateral inhibition within the locus coeruleus and control of transmitter release at the site of collateral inhibition.
Subject(s)
Receptors, Adrenergic/drug effects , Animals , Chlorpromazine/pharmacology , Clonidine/pharmacology , Desipramine/pharmacology , Male , Phenoxybenzamine/pharmacology , Piperoxan/pharmacology , Rats , Rats, Inbred Strains , Receptors, Adrenergic, alpha/drug effects , Secologanin Tryptamine Alkaloids/pharmacology , Sleep, REM/drug effectsABSTRACT
The present study investigated the mechanisms of the action of a tricyclic antidepressant, desmethylimipramine, upon paradoxical sleep in the rat in acute administration. Desmethylimipramine induces an increase in paradoxical sleep latency, as well as a decrease of its total duration; these two modifications are dose-dependent. Different mechanisms may be evoked: inhibition of catecholamine synthesis, inhibition of locus coeruleus by adrenergic collaterals, or an anticholinergic effect. The results show that inhibition of synthesis is not quantitatively sufficient to induce the observed effects. It appears more probable that this decrease in paradoxical sleep results from a collateral inhibition, with the possible participation of an anticholinergic effect. The contributions of these different factors are discussed.
Subject(s)
Desipramine/pharmacology , Sleep, REM/drug effects , Animals , Kinetics , Locus Coeruleus/drug effects , Locus Coeruleus/physiology , Male , Methyltyrosines/pharmacology , Rats , Rats, Inbred Strains , Tyrosine 3-Monooxygenase/antagonists & inhibitors , alpha-MethyltyrosineABSTRACT
A double-blind, randomized trial was performed with 51 patients suffering from focal ischemic lesions in the territory of the middle cerebral artery. Intravenous infusions of 10% glycerol in 0.9% NaCl--5% glucose solutions were administered twice daily for 6 days to 26 patients, and the same amount of NaCl--glucose solutions to 25 controls. Glycerol did not reduce mortality (9 deaths in each group). The functional recovery was assessed by repeated neurological examinations during the 4 month trial. Glycerol significantly improved global performances and motor and sensory functions in patients with moderate disability, but its effect on global performances was transient. The patients with severe disability were not improved at all.
Subject(s)
Cerebral Infarction/drug therapy , Glycerol/therapeutic use , Aged , Brain/physiopathology , Brain Edema/drug therapy , Cerebral Infarction/mortality , Cerebral Infarction/physiopathology , Clinical Trials as Topic , Double-Blind Method , Hemodynamics/drug effects , Humans , Infusions, Parenteral , Neurologic ExaminationABSTRACT
Intravenous administration of glycerol under double-blind conditions (25 g twice daily for 6 days) to 26 patients with cerebral infarction localized in the territory of the middle cerebral artery temporarily improved the clinical evolution, as assessed by a scoring system, in comparison with 25 patients receiving placebo infusions.
