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1.
J Neurochem ; 141(4): 614-625, 2017 05.
Article in English | MEDLINE | ID: mdl-28244186

ABSTRACT

Levodopa (l-DOPA, l-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to l-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe disease at baseline and higher daily l-DOPA dose, but biomarkers to predict the risk of motor complications are not yet available. Here, we investigated whether CSF levels of catecholamines and its metabolites are altered in PD patients with LID [PD-LID, n = 8)] as compared to non-dyskinetic PD patients receiving l-DOPA (PD-L, n = 6), or not receiving l-DOPA (PD-N, n = 7) as well as non-PD controls (n = 16). PD patients were clinically assessed using the Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale and CSF was collected after overnight fasting and 1-2 h after oral intake of l-DOPA or other anti-Parkinson medication. CSF catecholamines and its metabolites were analyzed by HPLC with electrochemical detection. We observed (i) decreased levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid in PD patients not receiving l-DOPA (ii) higher dopamine (DA) levels in PD-LID as compared to controls (iii) higher DA/l-DOPA and lower DOPAC/DA ratio's in PD-LID as compared to PD-L and (iv) an age-dependent increase of DA and decrease of DOPAC/DA ratio in controls. These results suggest increased DA release from non-DA cells and deficient DA re-uptake in PD-LID. Monitoring DA and DOPAC in CSF of l-DOPA-treated PD patients may help identify patients at risk of developing LID.


Subject(s)
Antiparkinson Agents/adverse effects , Antiparkinson Agents/therapeutic use , Catecholamines/cerebrospinal fluid , Dyskinesia, Drug-Induced/cerebrospinal fluid , Levodopa/adverse effects , Levodopa/therapeutic use , Parkinson Disease/cerebrospinal fluid , 3,4-Dihydroxyphenylacetic Acid/cerebrospinal fluid , Adult , Aged , Aging/cerebrospinal fluid , Dopamine/cerebrospinal fluid , Female , Homovanillic Acid/cerebrospinal fluid , Humans , Male , Middle Aged , Norepinephrine/cerebrospinal fluid
2.
Am J Psychiatry ; 155(9): 1207-13, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9734544

ABSTRACT

OBJECTIVE: Tardive dyskinesia is a movement disorder affecting 20%-40% of patients treated chronically with neuroleptic drugs. The dopamine supersensitivity hypothesis cannot account for the time course of tardive dyskinesia or for the persistence of tardive dyskinesia and the associated structural changes after neuroleptics are discontinued. The authors hypothesized that neuroleptics enhance striatal glutamatergic neurotransmission by blocking presynaptic dopamine receptors, which causes neuronal damage as a consequence of oxidative stress. METHOD: CSF was obtained from 20 patients with schizophrenia, 11 of whom had tardive dyskinesia. Markers for oxidative stress, including superoxide dismutase, lipid hydroperoxide, and protein carbonyl groups, and markers for excitatory neurotransmission, including N-acetylaspartate, N-acetylaspartylglutamate, aspartate, and glutamate, were measured in the CSF specimens. Patients were also rated for tardive dyskinesia symptoms with the Abnormal Involuntary Movement Scale. RESULTS: Tardive dyskinesia patients had significantly higher concentrations of N-acetylaspartate, N-acetylaspartylglutamate, and aspartate in their CSF than patients without tardive dyskinesia when age and neuroleptic dose were controlled for. The significance of the higher levels of protein-oxidized products associated with tardive dyskinesia did not pass Bonferroni correction, however. Tardive dyskinesia symptoms correlated positively with markers of excitatory neurotransmission and protein carbonyl group and negatively with CSF superoxide dismutase activity. CONCLUSIONS: These findings suggest that there are elevated levels of oxidative stress and glutamatergic neurotransmission in tardive dyskinesia, both of which may be relevant to the pathophysiology of tardive dyskinesia.


Subject(s)
Dyskinesia, Drug-Induced/physiopathology , Glutamates/physiology , Oxidative Stress/physiology , Synaptic Transmission/physiology , Adult , Antipsychotic Agents/adverse effects , Aspartic Acid/analogs & derivatives , Aspartic Acid/cerebrospinal fluid , Biomarkers , Corpus Striatum/drug effects , Corpus Striatum/physiopathology , Dipeptides/cerebrospinal fluid , Dopamine Antagonists/pharmacology , Dyskinesia, Drug-Induced/cerebrospinal fluid , Dyskinesia, Drug-Induced/etiology , Female , Glutamates/cerebrospinal fluid , Glutamates/pharmacology , Humans , Lipid Peroxides/cerebrospinal fluid , Male , Middle Aged , Neuropeptides/cerebrospinal fluid , Psychiatric Status Rating Scales/statistics & numerical data , Receptors, Dopamine/drug effects , Schizophrenia/cerebrospinal fluid , Schizophrenia/diagnosis , Schizophrenia/drug therapy , Superoxide Dismutase/cerebrospinal fluid , Synaptic Transmission/drug effects
3.
Am J Psychiatry ; 152(12): 1730-6, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8526238

ABSTRACT

OBJECTIVE: This study was undertaken to assess the relationships among CSF concentrations of substrates of mitochondrial energy metabolism, neuroleptic medication, and neurological side effects. METHOD: CSF was obtained from 25 patients with schizophrenia; seven were unmedicated and 11 had tardive dyskinesia. CSF concentrations of four substrates of mitochondrial energy metabolism (Krebs cycle)--alanine, aspartate, lactate, and pyruvate--were determined. Tardive dyskinesia was measured with the Abnormal Involuntary Movement Scale (AIMS), and parkinsonism was measured with the Simpson-Angus Rating Scale. RESULTS: CSF concentrations of alanine were significantly elevated in the medicated patients when tardive dyskinesia status was controlled for. CSF aspartate concentrations were significantly elevated in patients with tardive dyskinesia when medication status was controlled for and were significantly correlated with total scores on the AIMS. CONCLUSIONS: These results are consistent with a model linking neuroleptic-induced neurological side effects with impairment of mitochondrial energy metabolism, possibly mediated by inhibition of complex 1 of the electron transport chain.


Subject(s)
Antipsychotic Agents/adverse effects , Dyskinesia, Drug-Induced/cerebrospinal fluid , Energy Metabolism , Schizophrenia/drug therapy , Adult , Alanine/cerebrospinal fluid , Alanine/metabolism , Aspartic Acid/cerebrospinal fluid , Aspartic Acid/metabolism , Citric Acid Cycle , Dyskinesia, Drug-Induced/etiology , Dyskinesia, Drug-Induced/metabolism , Female , Humans , Lactates/cerebrospinal fluid , Lactates/metabolism , Male , Middle Aged , Mitochondria/metabolism , Oxidative Phosphorylation , Pyruvates/cerebrospinal fluid , Pyruvates/metabolism , Schizophrenia/metabolism
4.
Schizophr Res ; 14(2): 93-104, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7711000

ABSTRACT

Levels of the histamine metabolites, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), and metabolites of other aminergic transmitters and of norepinephrine were measured in cerebrospinal fluid of 36 inpatients with chronic schizophrenia and eight controls. The mean t-MH level from controls was nearly identical to the levels seen previously in healthy volunteers. Compared with controls, the mean level of t-MH in the schizophrenic patients was 2.6-fold higher (p = 0.006); 21 of the patients had levels exceeding the range of controls. There was no significant difference (p > 0.05) in levels of other analytes, although the levels of t-MH correlated significantly with those of t-MIAA, homovanillic acid, 3,4-dihydroxyphenylacetic acid, norepinephrine, 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid. The difference in levels of t-MH were not attributable to medication, since those taking (n = 10) or withdrawn from (n = 26) neuroleptic drugs had nearly the same mean levels of t-MH; each group had higher levels than controls (ANOVA: p < 0.05). Patients with or without tardive dyskinesia showed no significant differences in means of any analyte. Only levels of t-MH among those with schizophrenia correlated with positive symptom scores on the Psychiatric Symptom Assessment Scale (rs = 0.45, p < 0.02). The elevated levels of t-MH in cerebrospinal fluid, which represent histamine that was released and metabolized, suggest increased central histaminergic activity in patients with chronic schizophrenia.


Subject(s)
Histamine/cerebrospinal fluid , Neurotransmitter Agents/cerebrospinal fluid , Psychiatric Status Rating Scales , Schizophrenia/cerebrospinal fluid , Schizophrenic Psychology , Adult , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Biogenic Amines/cerebrospinal fluid , Chronic Disease , Dyskinesia, Drug-Induced/cerebrospinal fluid , Female , Humans , Imidazoles/cerebrospinal fluid , Male , Methylhistamines/cerebrospinal fluid , Middle Aged , Norepinephrine/cerebrospinal fluid , Reference Values , Schizophrenia/diagnosis , Schizophrenia/drug therapy
6.
Article in English | MEDLINE | ID: mdl-1349210

ABSTRACT

Occurrence of extrapyramidal signs was investigated in a follow-up study of 32 patients with probable Alzheimer's disease (AD). Bradykinesia and rigidity were observed in 39% and 11% of the neuroleptic-free patients at entry and in 72% and 61% at year 3, respectively. Tremor was not a predominant feature nor did its occurrence increase over time. Use of neuroleptics contributed to extrapyramidal signs; 75-100% of the neuroleptic-treated patients showed bradykinesia, rigidity or orofacial dyskinesia. The homovanillic acid (HVA) concentrations of the cerebrospinal fluid at entry were comparable to those of age-matched controls. Nor did HVA levels correlate with rigidity or bradykinesia in these early AD cases. Presence of bradykinesia or rigidity at the initial evaluation predicted more severe dementia and a poor prognosis over the period of 3 years, although interaction of initial clinical severity of dementia was significant. Of 15 patients with these signs 3 (20%) died and 8 (53%) needed institutional care, while of 17 patients without these signs only 1 (6%) died and 2 (12%) were institutionalized by year 3 (p less than 0.01).


Subject(s)
Alzheimer Disease/complications , Basal Ganglia Diseases/etiology , Aged , Aged, 80 and over , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/epidemiology , Alzheimer Disease/mortality , Antipsychotic Agents/adverse effects , Basal Ganglia Diseases/cerebrospinal fluid , Basal Ganglia Diseases/epidemiology , Dopamine/metabolism , Dyskinesia, Drug-Induced/cerebrospinal fluid , Dyskinesia, Drug-Induced/epidemiology , Dyskinesia, Drug-Induced/etiology , Female , Follow-Up Studies , Homovanillic Acid/cerebrospinal fluid , Humans , Incidence , Institutionalization/statistics & numerical data , Male , Middle Aged , Muscle Rigidity/cerebrospinal fluid , Muscle Rigidity/epidemiology , Muscle Rigidity/etiology , Predictive Value of Tests , Prognosis , Severity of Illness Index
9.
Biol Psychiatry ; 25(2): 200-6, 1989 Jan 15.
Article in English | MEDLINE | ID: mdl-2564786

ABSTRACT

We measured the contents of gamma-aminobutyric acid (GABA) and of other amino compounds in five regions of autopsied brain from 18 patients with schizophrenia and from a large group of adult control subjects dying without any neurological or psychiatric disorder. In addition, concentrations of GABA were measured in the cerebrospinal fluid (CSF) of living schizophrenic patients and control subjects. No deficiency of GABA was found in the frontal cortex, caudate nucleus, putamen, nucleus accumbens, or medial dorsal thalamus of patients dying with schizophrenia, nor were GABA concentrations low in the CSF of living schizophrenic patients. These results do not confirm our earlier report of low levels of GABA in the nucleus accumbens and thalamus of some schizophrenic patients. We do not find neurochemical evidence favoring an involvement of GABAergic neuronal hypofunction in the etiology either of schizophrenia or of neuroleptic-induced tardive dyskinesia.


Subject(s)
Brain/metabolism , Dyskinesia, Drug-Induced/cerebrospinal fluid , Schizophrenia/cerebrospinal fluid , gamma-Aminobutyric Acid/cerebrospinal fluid , Adult , Aged , Aged, 80 and over , Antipsychotic Agents/adverse effects , Brain/drug effects , Female , Humans , Male , Middle Aged , Receptors, GABA-A/drug effects
10.
Psychopharmacology (Berl) ; 99 Suppl: S54-9, 1989.
Article in English | MEDLINE | ID: mdl-2479047

ABSTRACT

Clozapine, an atypical neuroleptic, does not cause extrapyramidal symptoms of Parkinsonism and dystonia and appears to have a reduced or absent capacity to produce tardive dyskinesia. 37 subjects, most with chronic schizophrenia, were treated with clozapine and TD outcome was analyzed. A subset of these subjects underwent plasma and CSF studies. TD response was heterogenous, but a proportion of patients improved with clozapine treatment. Neurochemical data differed from published reports of classical neuroleptics with the most robust effect produced by clozapine seen in CSF norepinephrine levels. Other neurochemical data and implications for the mechanism of clozapine in TD are reviewed.


Subject(s)
Clozapine/adverse effects , Dibenzazepines/adverse effects , Dyskinesia, Drug-Induced/physiopathology , Adolescent , Adult , Clozapine/therapeutic use , Dyskinesia, Drug-Induced/cerebrospinal fluid , Epinephrine/cerebrospinal fluid , Female , Homovanillic Acid/cerebrospinal fluid , Humans , Hydroxyindoleacetic Acid/cerebrospinal fluid , Male , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Norepinephrine/cerebrospinal fluid , Phenethylamines/cerebrospinal fluid , Prolactin/blood , Schizophrenia/drug therapy
11.
Mov Disord ; 3(2): 133-9, 1988.
Article in English | MEDLINE | ID: mdl-3221901

ABSTRACT

The effect of isoniazid on levodopa-induced dyskinesias has been evaluated in 20 patients with Parkinson's disease, following a serendipitous observation that choreic dyskinesias induced by levodopa in one parkinsonian patient were markedly reduced during treatment with isoniazid for tuberculous infection. A mean average isoniazid dose of 290 mg was given without any change in current antiparkinsonian treatment. "Benefit of dose" choreic dyskinesias were markedly reduced in 18 patients within the first few weeks of treatment. This effect was accompanied by an intolerable worsening of parkinsonian signs. All patients returned to their basal situation after isoniazid interferes with the therapeutic action of levodopa and dopamine agonists. The precise mechanism by which this action occurred is not known, but several possible explanations are discussed.


Subject(s)
Dyskinesia, Drug-Induced/drug therapy , Isoniazid/therapeutic use , Levodopa/adverse effects , Parkinson Disease/complications , Aged , Dyskinesia, Drug-Induced/cerebrospinal fluid , Dyskinesia, Drug-Induced/etiology , Female , Humans , Isoniazid/cerebrospinal fluid , Isoniazid/pharmacokinetics , Male , Middle Aged , Parkinson Disease/drug therapy
12.
J Neurol Neurosurg Psychiatry ; 50(12): 1674-8, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3437301

ABSTRACT

Clinical and biochemical effects of Gamma-vinyl-Gaba (GVG) have been evaluated in a blind video-controlled study in 10 psychiatric patients (mean age 71 yr) with tardive dyskinesia. CSF free and total Gaba and homocarnosine concentrations increased from three to five fold with GVG treatment. Despite the GVG-induced biological effects on Gaba metabolism, GVG did not consistently improve tardive dyskinesia. Psychomotor side-effects occurred in older patients, who only tolerated GVG dosages of 2-4 g/day.


Subject(s)
Aminocaproates/therapeutic use , Dyskinesia, Drug-Induced/drug therapy , Aged , Aminocaproates/adverse effects , Carnosine/analogs & derivatives , Carnosine/cerebrospinal fluid , Dyskinesia, Drug-Induced/cerebrospinal fluid , Dyskinesia, Drug-Induced/physiopathology , Humans , Mental Disorders/cerebrospinal fluid , Mental Disorders/physiopathology , Vigabatrin , gamma-Aminobutyric Acid/cerebrospinal fluid
13.
Neurol Neurochir Pol ; 19(5): 401-3, 1985.
Article in Polish | MEDLINE | ID: mdl-2421191

ABSTRACT

The concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were determined in the cerebrospinal fluid in 17 patients with Parkinson's disease and 10 controls. The patients with Parkinson's disease were on long-term treatment with L-DOPA preparations. In 9 of them drug-induced dyskineses were observed. The HVA/5-HIAA ratio was determined in the cerebrospinal fluid separately in cases with dyskineses, in cases without dyskineses and in controls. It was found that this ratio was significantly higher in patients with drug-induced dyskineses as compared to patients without dyskineses, and especially to controls. It is suggested that this may mean that in cases of drug-induced dyskineses disturbances exist in the equilibrium between the dopaminergic and serotoninergic systems in favour of the former, which may be one of the causes of involuntary movements.


Subject(s)
Carbidopa/adverse effects , Dyskinesia, Drug-Induced/cerebrospinal fluid , Homovanillic Acid/cerebrospinal fluid , Hydroxyindoleacetic Acid/cerebrospinal fluid , Levodopa/adverse effects , Parkinson Disease/drug therapy , Aged , Carbidopa/therapeutic use , Drug Combinations/adverse effects , Drug Combinations/therapeutic use , Female , Humans , Levodopa/therapeutic use , Male , Middle Aged , Parkinson Disease/cerebrospinal fluid
14.
Neurosci Lett ; 58(3): 327-31, 1985 Aug 05.
Article in English | MEDLINE | ID: mdl-2995879

ABSTRACT

In 4 ovariectomized monkeys bearing a dopamine-sensitive lingual dyskinesia due to a previous mid-brain lesion, 30 ng of 17 beta-estradiol injected subcutaneously, caused a 4-fold increase in the dyskinesia in the hour following the injection. In a separate experiment done on 7 anesthetized monkeys, the same dose of estradiol caused a significant increase of homovanillic acid in the cerebrospinal fluid obtained by cisternal puncture. The above findings suggest that very small doses of estradiol in the physiological range can increase dopaminergic transmission in the striatum via increased release.


Subject(s)
Dyskinesia, Drug-Induced/etiology , Estradiol/toxicity , Homovanillic Acid/cerebrospinal fluid , Animals , Corpus Striatum/drug effects , Dopamine/physiology , Dyskinesia, Drug-Induced/cerebrospinal fluid , Female , Macaca fascicularis , Synaptic Transmission/drug effects , Tongue Diseases/chemically induced
15.
Arch Neurol ; 42(2): 166-9, 1985 Feb.
Article in English | MEDLINE | ID: mdl-2579626

ABSTRACT

We measured four monoamine metabolite levels in CSF before and after probenecid administration to normal controls and to patients with Huntington's disease (HD), dystonia, and tardive dyskinesia. We identified differences only for the dopamine metabolite homovanillic acid (HVA), which showed increased baseline values and decreased turnover in normal aging, but decreased baseline values and normal turnover in HD. These results suggest that dopamine neurons are linked both to normal aging and to HD and that CSF HVA studies can distinguish differences in the functioning of dopamine neurons in normal aging and HD.


Subject(s)
3,4-Dihydroxyphenylacetic Acid/cerebrospinal fluid , Dyskinesia, Drug-Induced/cerebrospinal fluid , Dystonia/cerebrospinal fluid , Glycols/cerebrospinal fluid , Homovanillic Acid/cerebrospinal fluid , Hydroxyindoleacetic Acid/cerebrospinal fluid , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Parkinson Disease/cerebrospinal fluid , Phenylacetates/cerebrospinal fluid , Adult , Aged , Female , Humans , Male , Middle Aged
16.
Folia Psychiatr Neurol Jpn ; 39(2): 147-53, 1985.
Article in English | MEDLINE | ID: mdl-2866149

ABSTRACT

Calcium-hopantenate (HOPA), a derivative of GABA, was administered to 9 psychiatric patients with neuroleptics-induced tardive dyskinesia. In a clinical study, involuntary movements have improved significantly after a 4-8-week medication. Although there was no correlation between the cerebrospinal fluid (CSF) levels of HOPA, GABA, HVA or clinical response, the CSF HOPA levels significantly correlated with changes in the CSF GABA levels. These results suggest that HOPA alleviates the symptoms of tardive dyskinesia being mediated by the central GABAergic mechanisms.


Subject(s)
Antipsychotic Agents/adverse effects , Dyskinesia, Drug-Induced/drug therapy , Pantothenic Acid/analogs & derivatives , gamma-Aminobutyric Acid/analogs & derivatives , Adult , Dyskinesia, Drug-Induced/cerebrospinal fluid , Humans , Male , Middle Aged , Pantothenic Acid/cerebrospinal fluid , Pantothenic Acid/therapeutic use , gamma-Aminobutyric Acid/cerebrospinal fluid , gamma-Aminobutyric Acid/therapeutic use
17.
Psychiatry Res ; 11(4): 347-51, 1984 Apr.
Article in English | MEDLINE | ID: mdl-6146151

ABSTRACT

Cerebrospinal fluid (CSF) homovanillic acid (HVA), cyclic adenosine 3', 5'-monophosphate (cAMP), and serum prolactin were measured in schizophrenic male patients with tardive dyskinesia (TD) and in those exhibiting the symptoms of chronic neuroleptic parkinsonism (P). The patients (nine TD and eight P) were chronic paranoid schizophrenics. Levels of HVA in CSF were found to be significantly higher in the TD group. Normal prolactin levels were observed in both groups and are indicative of tolerance developed in the hypothalamic tuberoinfundibular dopaminergic system.


Subject(s)
Cyclic AMP/cerebrospinal fluid , Dyskinesia, Drug-Induced/cerebrospinal fluid , Homovanillic Acid/cerebrospinal fluid , Parkinson Disease, Secondary/cerebrospinal fluid , Phenylacetates/cerebrospinal fluid , Prolactin/blood , Adult , Antipsychotic Agents/adverse effects , Dyskinesia, Drug-Induced/blood , Dyskinesia, Drug-Induced/etiology , Humans , Male , Middle Aged , Parkinson Disease, Secondary/blood , Parkinson Disease, Secondary/chemically induced , Schizophrenia, Paranoid/drug therapy
18.
Br J Psychiatry ; 144: 177-80, 1984 Feb.
Article in English | MEDLINE | ID: mdl-6200172

ABSTRACT

Cerebrospinal fluid was collected from 28 psychiatric (mostly schizophrenic) inpatients from Bombay, India. These included eight patients with tardive dyskinesia, five with spontaneous dyskinesia and 15 without dyskinesia. The samples were flown to the National Institute of Mental Health, Washington, D.C., where they were analyzed "blind" for concentrations of noradrenaline and several monoamine metabolites. Patients with tardive dyskinesia had significantly higher noradrenaline concentrations in the CSF as compared with the other two groups. Spontaneous dyskinesia group had significantly lower concentrations of homovanillic acid in the CSF. Our results support the hypothesis of noradrenergic hyperactivity, rather than postsynaptic dopamine receptor supersensitivity, in tardive dyskinesia.


Subject(s)
Dyskinesia, Drug-Induced/cerebrospinal fluid , Norepinephrine/cerebrospinal fluid , 3,4-Dihydroxyphenylacetic Acid/cerebrospinal fluid , Adult , Aged , Antipsychotic Agents/therapeutic use , Homovanillic Acid/cerebrospinal fluid , Humans , Hydroxyindoleacetic Acid/cerebrospinal fluid , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Middle Aged , Movement Disorders/cerebrospinal fluid , Schizophrenia/cerebrospinal fluid
19.
Clin Ther ; 7 Spec No: 1-17, 1984.
Article in English | MEDLINE | ID: mdl-6085032

ABSTRACT

Lumbar cerebrospinal fluid (CSF) homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), cyclic AMP (cAMP) and cyclic GMP (cGMP) were measured in chronic schizophrenics with tardive dyskinesia before and three weeks after the initial treatment with sodium valproate (VPA), cyproheptadine, oxypertine or hydroxyzine pamoate. HVA levels significantly decreased after the administration of VPA, cyproheptadine or oxypertine. Cyclic GMP levels significantly increased after the administration of VPA or cyproheptadine. Elevation of the cAMP level was observed after the administration of VPA, cyproheptadine or oxypertine. An elevation of the MHPG level was observed during oxypertine treatment and a reduction of the 5-HIAA level was observed during hydroxyzine pamoate treatment. Decreases in HVA and increases in cGMP levels during treatment might be indicative of normalization of the dopaminergic-cholinergic imbalance in the brain. Lumbar CSF HVA and gamma-aminobutyric acid (GABA) were also measured in patients with tardive dyskinesia before and eight weeks after Ca-hopantenate treatment. No significant changes were observed before or after this treatment. The hypothesis is discussed that the pathogenesis of tardive dyskinesia may involve functional disorders not only of the dopaminergic or cholinergic system but also of the norepinephrinergic, serotoninergic and GABA-ergic systems.


Subject(s)
Cyproheptadine/therapeutic use , Dyskinesia, Drug-Induced/drug therapy , Hydroxyzine/therapeutic use , Indoles/therapeutic use , Piperazines/therapeutic use , Valproic Acid/therapeutic use , Adult , Aged , Cyclic AMP/cerebrospinal fluid , Cyclic GMP/cerebrospinal fluid , Dyskinesia, Drug-Induced/cerebrospinal fluid , Female , Homovanillic Acid/cerebrospinal fluid , Humans , Hydroxyindoleacetic Acid/cerebrospinal fluid , Male , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Middle Aged
20.
Folia Psychiatr Neurol Jpn ; 37(2): 129-35, 1983.
Article in English | MEDLINE | ID: mdl-6200411

ABSTRACT

Cerebrospinal fluid (CSF) HVA, MHPG, 5-HIAA, cAMP and cGMP concentrations were measured in schizophrenic patients with tardive dyskinesia before and after a three-week administration of oxypertine (n = 4), hydroxyzine pamoate (n = 4) or placebo (n = 4). The oxypertine administration resulted in a reduction of the CSF HVA concentration and an elevation of the MHPG and cAMP concentrations, associated with a clinical improvement in tardive dyskinesia. The hydroxyzine administration reduced the CSF 5-HIAA concentration in all the patients and the CSF HVA concentration in two of four patients with a clinical improvement. A reduction in the CSF HVA concentration associated with possible therapeutic effects of oxypertine or hydroxyzine may suggest the normalization of a hyperdopaminergic state. Discussions were held that functional disorders of not only the dopaminergic system but the norepinephrinergic and serotoninergic systems may relate to the pathogenesis of tardive dyskinesia.


Subject(s)
Biogenic Amines/cerebrospinal fluid , Dyskinesia, Drug-Induced/drug therapy , Hydroxyzine/therapeutic use , Indoles/therapeutic use , Piperazines/therapeutic use , Clinical Trials as Topic , Cyclic AMP/cerebrospinal fluid , Cyclic GMP/cerebrospinal fluid , Dyskinesia, Drug-Induced/cerebrospinal fluid , Female , Homovanillic Acid/cerebrospinal fluid , Humans , Hydroxyindoleacetic Acid/cerebrospinal fluid , Male , Methoxyhydroxyphenylglycol/cerebrospinal fluid
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