cyclic-gmp and Tremor

Topics: Alkaloids; Animals; Cats; Cerebellar Nuclei; Cerebellum; Cyclic GMP; Diazepam; Dopamine; Electroencephalography; gamma-Aminobutyric Acid; Harmaline; Harmine; Levodopa; Medulla Oblongata; Neural Pathways; Olivary Nucleus; Rabbits; Spinal Cord; Synaptic Transmission; Tremor

Topics: Aminobutyrates; Animals; Anti-Anxiety Agents; Benzodiazepines; Cerebellum; Cyclic GMP; gamma-Aminobutyric Acid; Glutamates; Harmaline; Isoniazid; Mice; Neurons; Purkinje Cells; Rats; Seizures; Tremor

Administration to mice of harmaline (100 mg/kg SC) resulted in a greater than two-fold increase in cyclic GMP in the cerebellum 15 min later. This response was inhibited by pretreatment 5 min before the harmaline with pentobarbital (ED50 6.5 mg/kg), chlormethiazole (ED50 10.4 mg/kg) and dizocilpine (ED50 0.5 mg/kg). Harmaline-induced tremor was inhibited by pentobarbital (ED50 30 mg/kg) and chlormethiazole (ED50 50 mg/kg) but not dizocilpine. The data demonstrate that the harmaline-induced tremor and cerebellar cyclic GMP rise are probably not associated. They also demonstrate that chlormethiazole is able to inhibit a biochemical response (the increase in cerebellar cyclic GMP) which results from increased glutamate function.

Topics: Animals; Cerebellum; Chlormethiazole; Cyclic GMP; Dizocilpine Maleate; Harmaline; Male; Mice; Mice, Inbred Strains; Pentobarbital; Tremor

Administration of the beta-carboline alkaloid, harmaline, causes the neurons of the inferior olive to fire synchronously and to act as a pacemaker for the generation of tremor. Rats treated daily with harmaline showed a progressive loss of drug-induced tremor. This tolerance was long-lasting and specific. No cross-tolerance was noted to the drug oxotremorine. Prevention or attenuation of tremor by pretreatment with diazepam or morphine preserved the tremorogenic capacity of harmaline when administered alone. These results suggest a relatively permanent change in the olivo-cerebello-bulbar pathway that underlies the generation of tremor induced by harmaline. Treatment with harmaline also increased cyclic 3',5'-guanosine monophosphate (cGMP) in the cerebellum, presumably through activation of the climbing fiber pathway from the inferior olive to the cerebellar cortex. These increases were attenuated after repeated treatment. These results suggest that the site of tolerance to the tremogenic effects of harmaline lies within the olivo-cerebellar system.

Topics: Alkaloids; Animals; Cerebellum; Cyclic GMP; Diazepam; Drug Tolerance; Harmaline; Morphine; Olivary Nucleus; Rats; Rats, Inbred Strains; Time Factors; Tremor

Concentrations of cyclic nucleotides--adenosine-3',5'-monophosphate (c-AMP) and guanosine-3',5'-monophosphate (c-GMP)--were measured in cerebrospinal fluid (CSF) of 17 drug-free Parkinson patients and 12 controls. No significant difference between the cyclic nucleotide contents (p greater than 0.05) in CSF of patients and controls was detected, nor was there a correlation between the content and the degree of neurological disability. Besides, no changes in the cyclic nucleotide contents were detected in the subgroups of patients according to the prominence of tremor or rigidity/akinesia as the main symptoms of the disease.

Topics: Cyclic AMP; Cyclic GMP; Female; Humans; Male; Middle Aged; Movement Disorders; Muscle Rigidity; Parkinson Disease; Tremor

Alaproclate (10-60 mg/kg) injected i.p. into male mice potentiated and prolonged the oxotremorine and physostigmine-induced tremor in a dose-dependent manner. Atropine completely blocked the tremor caused by oxotremorine or physostigmine both in the presence and absence of alaproclate. Pretreatment with the 5-HT receptor antagonist metitepine completely blocked the enhancement of oxotremorine-induced tremor caused by alaproclate. Biochemical studies indicated that the above effects cannot be explained by assuming that alaproclate a) acts as a cholinergic agonist, b) inhibits the acetylcholine esterase, c) interferes with choline uptake or acetylcholine synthesis, or d) directly potentiates the release of acetylcholine. In ligand binding studies alaproclate was found to be a weak competitive inhibitor of muscarinic antagonist binding to membranes from the rat cerebral cortex, rat striatum, human cerebral cortex and human striatum. (Ki approximately 28-40 microM in all four tissues). The present results suggest that alaproclate may potentiate muscarinic responses by a mechanism involving serotonergic receptor mechanisms rather than by a direct interaction with the muscarinic cholinergic receptors.

Topics: Alanine; Animals; Brain; Cyclic GMP; Drug Synergism; Hippocampus; Male; Mice; Oxotremorine; Physostigmine; Rats; Rats, Inbred Strains; Receptors, Muscarinic; Receptors, Serotonin; Tremor

The dystonic rat (dt) is an autosomal recessive mutant displaying a complex motor syndrome that includes sustained axial twisting movements. The syndrome is correlated with increased glutamic acid decarboxylase activity in the deep cerebellar nuclei and increased cerebellar norepinephrine levels in comparison with phenotypically normal littermates. Biochemical, behavioral, and anatomical techniques were used to investigate the possibility that the abnormalities noted in the cerebellum of the dt rat were indicative of altered function of the major projection neurons of the cerebellar cortex, the Purkinje cells. Phenotypically normal rats showed tremor in response to harmaline, a drug that acts on the inferior olive to produce bursting in the climbing fiber pathway. Dystonic rats were insensitive to the effects of harmaline but did respond to oxotremorine. Levels of the cyclic nucleotide 3',5'-cyclic guanosine monophosphate, a biochemical marker for Purkinje cells, increased in response to harmaline in normal rats but were significantly lower in dystonic rats under both basal and harmaline-stimulated conditions. Purkinje cell soma size was reduced in the dystonic rats but no other morphological correlates of the behavioral or biochemical deficits were noted. Taken together with other observations on this mutant, the results suggest an impairment in the cerebellum or in its connections with lower brainstem and spinal cord sites.

Topics: Alkaloids; Animals; Behavior, Animal; Cerebellum; Cyclic GMP; Drug Resistance; Dystonia; Harmaline; Oxotremorine; Purkinje Cells; Rats; Rats, Mutant Strains; Tremor

The spectra of pharmacological effects of ethanol and the benzodiazepine show a degree of overlap. Neurophysiological and neurochemical evidence indicates that both ethanol and benzodiazepines facilitate inhibitory neurotransmission mediated by GABA. Diazepam has been reported to inhibit both the tremor and mechanism of cerebellar cyclic GMP caused by harmaline by a neurotransmission in the cerebellum. Because of the similarities between ethanol and benzodiazepines, the effects of ethanol on harmaline-induced tremor and increase of cerebellar cyclic GMP were studied. Ethanol inhibited harmaline-induced tremor at doses as low as 0.1 g/kg. At this low dose, however, a dissociation between inhibition of harmaline tremor and inhibition of the harmaline-induced increase of cerebellar cyclic GMP was observed.

Topics: Alkaloids; Animals; Cerebellum; Cyclic GMP; Diazepam; Dose-Response Relationship, Drug; Ethanol; Harmaline; Male; Mice; Mice, Inbred C57BL; Oxotremorine; Purkinje Cells; Tremor

Lumbar CSF HVA, MHPG, 5HIAA, cAMP, and cGMP were measured in 12 chronic schizophrenics with tardive dyskinesia before and 3 weeks after sodium valproate (VPA) or cyproheptadine treatment. HVA levels significantly decreased and cAMP and cGMP levels significantly increased during the administration of VPA or cyproheptadine. There were no significant correlations between the degree of improvement in tardive dyskinesia and the changes of amine metabolities or cyclic nucleotides. None of the pretreatment values for CSF amine metabolites or cyclic nucleotides were different from those of 15 chronic schizophrenics without tardive dyskinesia as controls. Decrease of HVA and increase of cGMP during the treatment might indicate the normalization of dopaminergic-cholinergic imbalance in the brain. Furthermore, significantly low levels of 5HIAA were observed in the patients with drug-induced tremor. It is suggested that neuroleptic-induced tremor may be attributed to serotonergic dysfunction in the brain.

Topics: Adult; Chronic Disease; Cyclic AMP; Cyclic GMP; Cyproheptadine; Dyskinesia, Drug-Induced; Female; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Middle Aged; Neurotransmitter Agents; Schizophrenia; Tremor; Valproic Acid

Cyclic GMP levels were dose-dependently increased by excitatory drugs such as picrotoxin, pentetrazol, oxotremorine and harmaline in mouse cerebellum and medial forebrain (parts of the cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) in vivo. Cyclic AMP levels remained unchanged under these conditions. Pretreatment with diazepam completely abolished the effect of picrotoxin and harmaline and significantly reduced the effects of pentetrazol and oxotremorine on cyclic GMP levels, but the tremor due to harmaline and oxotremorine was not blocked. Pretreatment with pentobarbital also prevented or strongly reduced changes in cyclic GMP levels elicited by excitatory drugs without abolishing the tremorigenic effects of harmaline and oxotremorine. Pretreatment with atropine was only effective in blocking cyclic GMP rise and tremor induced by oxotremorine and picrotoxin. Since pentobarbital and diazepam also decreased cyclic GMP levels in a dose-dependent manner in brains of control animals, the changes in cyclic GMP levels observed after administration of excitatory drugs appear to be related to the arousal reaction of the central nervous system.

Topics: Animals; Atropine; Brain; Brain Chemistry; Convulsants; Cyclic AMP; Cyclic GMP; Diazepam; Drug Interactions; gamma-Aminobutyric Acid; Harmaline; Male; Mice; Oxotremorine; Pentobarbital; Pentylenetetrazole; Picrotoxin; Tremor

Topics: Animals; Cerebellum; Cyclic AMP; Cyclic GMP; Male; Pentylenetetrazole; Prostaglandins E; Rats; Seizures; Tremor

Topics: Alkaloids; Animals; Binding Sites; Cerebellum; Cyclic GMP; Diazepam; Dose-Response Relationship, Drug; Indoles; Male; Monoamine Oxidase Inhibitors; Oxotremorine; Purkinje Cells; Pyridines; Rats; Tremor

Topics: Alkaloids; Animals; Brain Chemistry; Cerebellar Cortex; Cyclic GMP; Glutamates; Harmaline; Male; Oxotremorine; Pyridines; Rats; Tremor