Treatment of refractory amblyopia with levodopa associated with full-time occlusion in the dominant eye / Tratamento da ambliopia refratária com o uso de levodopa associada à oclusão total do olho dominante

Abstract Purpose: To evaluate visual outcomes of levodopa treatment associated with full occlusion of the dominant eye in patients with refractory amblyopia. Methods: A prospective study of 19 attended patients who were subject to treatment with Levodopa and Carbidopa on doses of 0.7mg/kg/day, a ratio of 4:1 divided into three daily doses for 5 weeks, combined with full occlusion (24 hours/day) of the dominant eye. The ophthalmologic exam from previous consultations up to treatment and after 8 weeks of therapy were collected from medical record data. Patients who had completed treatment for more than 12 months were included for complete eye examination. Results: The mean age before treatment with levodopa was 11.0 ± 4.2 years old (varying from 7 to 23 years). The best-corrected visual acuity (Snellen chart) of the amblyopic eye before treatment was 0.24 (0.6 in logMAR) ± 0.16, after 8 weeks of treatment it was 0.47(0.3 in logMAR) ± 0.33, while during the final evaluation it was 0.46 (0.3 in logMAR) ± 0.34. There was a statistically significant improvement in vision after 8 weeks of therapy which was maintained until the final evaluation (p = 0.007). Conclusion: Levodopa/Carbidopa therapyat doses of 0.7 mg/kg/day at a ratio of 4:1 divided in three daily doses, associated with full occlusion of the dominant eye during 5 weeks had a significant improvement on the visual acuity of the amblyopic eye, and persisted up to 1 year after the treatment.

Resumo Objetivo: Avaliar os resultados visuais do tratamento com levodopa associada à oclusão total do olho dominante em pacientes amblíopes. Métodos: Estudo prospectivo de 19 pacientes atendidos e submetidos ao tratamento com levodopa e carbidopa na dose de 0,7 mg/kg/dia e proporção de 4:1, divididos em três doses diárias, durante cinco semanas, combinada a oclusão total (24 horas/dia) do olho dominante. Foram coletados dados do prontuário referentes ao exame oftalmológico da consulta anterior ao tratamento e após 8 semanas de terapia. Os pacientes com término do tratamento com mais de 12 meses foram reconvocados para exame oftalmológico completo. Resultados: A média de idade dos pacientes previamente ao tratamento com levodopa foi de 11,0 ± 4,2 anos (variando de 7 a 23 anos). A acuidade visual melhor corrigida (Snellen) do olho amblíope antes do tratamento foi de 0,24 (0,6 em logMAR) ± 0,16, após 8 semanas de tratamento foi de 0,47 (0,3 em logMAR) ± 0,33 e na avaliação final foi de 0,46 (0,3 em logMAR) ± 0,34. Houve melhora estatisticamente significante da visão após 8 semanas de tratamento que se manteve até a avaliação final (p = 0,007) Conclusão: A terapia com levodopa/carbidopa em doses de 0,7mg/kg/dia na proporção de 4:1 dividida em três doses diárias, associada à oclusão total do olho dominante durante 5 semanas, apresentou uma melhora significativa na acuidade visual do olho ambliópico e persistiu até 1 ano após o tratamento.

Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Apomorphine in the treatment of Parkinson's disease: a review / O uso da apomorfina no tratamento da doença de Parkinson: revisão da literatura

ABSTRACT Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic tenet of this task entails tailored therapy, allowing for optimal motor function with the fewest adverse effects. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations, with potential positive effects on nonmotor symptoms, is the only antiparkinsonian agent whose capacity to control motor symptoms is comparable to that of levodopa. Subcutaneous administration, either as an intermittent injection or as continuous infusion, appears to be the most effective and tolerable route. This review summarizes the historical background, structure, mechanism of action, indications, contraindications and side effects, compares apomorphine infusion therapy with other treatments, such as oral therapy, deep brain stimulation and continuous enteral infusion of levodopa/carbidopa gel, and gives practical instructions on how to initiate treatment.

RESUMO A optimização do tratamento da doença de Parkinson idiopática se faz um desafio, pois tem impacto direto na qualidade de vida do paciente. O melhor esquema terapêutico é o que permite o melhor controle motor com os menores efeitos adversos, através de terapêutica individualizada. A apomorfina é o único medicamento antiparkinsoniano que pode ser comparável à potência da levodopa no controle dos sintomas motores. Trata-se de um agonista dopaminérgico empregado na terapia de resgate em pacientes com flutuações motoras e também contribui para a melhora de muitos sintomas não motores. A via subcutânea, com injeções intermitentes, ou com infusão contínua, parece ser a melhor opção pela eficácia e tolerabilidade. Essa revisão resume aspectos históricos, estrutura da molécula, mecanismo de ação, indicação, contra-indicação e efeitos colaterais, compara a terapia de infusão com apomorfina com outros tratamentos, como a terapia oral, estimulação cerebral profunda e infusão enteral contínua de levodopa/carbidopa gel, e fornece instruções práticas de como iniciar o tratamento.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Liquid Levodopa/Carbidopa: Old Solution, Forgotten Complication

No abstract available.

Levodopa+carbidopa in x-linked dystonia parkinsonism (XDP/DYT3/Lubag): A randomized, double-blind, placebo-controlled trial

@#<p><strong>OBJECTIVE:</strong> X-linked dystonia parkinsonism (XDP) is an adult-onset, progressive and debilitating movement disorder described among Filipino males from Panay Island. The available oral medications have been ineffective. While chemodenervation with botulinum toxin A works and deep brain stimulation surgery is promising, these are not affordable for the vast majority of patients. Thus, we decided to look into the efficacy, safety and tolerability of levodopa+carbidopa (levodopa) versus placebo among patients with XDP.</p><p><strong>METHODS:</strong> This was a double blind, randomized, placebo-controlled clinical trial. Patients were randomized to receive levodopa or placebo for 6 months. The dose was increased gradually until 1000 mg levodopa/day is reached or until side effects appear.</p><p><strong>RESULTS:</strong> A total of 86 out of 94 randomized patients (91.5%) were included in the intention-to-treat cohort for the primary efficacy analysis. Nineteen patients (9 in levodopa, 10 in placebo) dropped out or were lost to follow up. There was no significant difference in the baseline and last visit Burke Fahn Marsden Dystonia Rating Scale and the part III of the Unified Parkinson's Disease Rating Scale scores between levodopa and placebo. The most common adverse events in the levodopa group were increased movements, pain and nausea/ vomiting.</p><p><strong>CONCLUSION:</strong> While levodopa is safe and well-tolerated, it does not have any effect in alleviating the dystonia or parkinsonism in XDP.</p>

Anti-Allodynic Effects of Levodopa in Neuropathic Rats

PURPOSE: Levodopa is the most effective anti-Parkinsonian agent. It has also been known to exhibit analgesic properties in laboratory and clinical settings. However, studies evaluating its effects on neuropathic pain are limited. The aim of the present study was to examine the anti-allodynic effects of levodopa in neuropathic rats. MATERIALS AND METHODS: Sprague-Dawley male rats underwent the surgical procedure for L5 and L6 spinal nerves ligation. Sixty neuropathic rats were randomly divided into 6 groups for the oral administration of distilled water and levodopa at 10, 30, 50, 70, and 100 mg/kg, respectively. We co-administered carbidopa with levodopa to prevent peripheral synthesis of dopamine from levodopa, and observed tactile, cold, and heat allodynia pre-administration, and at 15, 30, 60, 90, 120, 150, 180, and 240 min after drug administration. We also measured locomotor function of neuropathic rats using rotarod test to examine whether levodopa caused side effects or not. RESULTS: Distilled water group didn't show any difference in all allodynia. For the levodopa groups (10-100 mg/kg), tactile and heat withdrawal thresholds were increased, and cold withdrawal frequency was decreased dose-dependently (p0.05). CONCLUSION: Levodopa reversed tactile, cold and heat allodynia in neuropathic rat without any side effects.

Experience with zolpidem in childhood dystonia

OBJECTIVES: To present a case of childhood primary dystonia with good response to zolpidem. INTRODUCTION: Dystonia is a syndrome of sustained muscle contractions causing twisting and repetitive movements or abnormal postures. It is not uncommon in children. Although there are several options to treat dystonia,its medical treatment is notoriously difficult and often unsuccessful. Zolpidem, an imidazopyridine agonist with a high affinity to benzodiazepine subtype receptor BZ1, is reported to improve basal ganglia disease including Parkinson'sdisease and various types of dystonia. THE CASE: 11 year old female with torticollis starting the 7years old. At q10years old symptoms progressed with her back hyperexteded. Her cranial MRI was normal. She was started on Levodopa and carbidopa however no improvement of symptoms was noted. She was started on zolpidem and there was a marked improvement in speech, writing, swallowing, walking and posture observed. DISCUSSION: Primary dystonia is defined as syndromes in which dystonia is the sole phenotypic manifestation. There is no cognitive decline and cranial MRI is normal. Management of childhood dystonia differs in certain respects from that of adult dystonia. Dopamine responsive dystonia in children is rare, but a trial of L-dopa should be performed on all patients rith childhood-onset dystonia. Dystonia is associated with hypoactivity of the globus pallidus interna, and widespread brain alterations in GABAA/benzodiazepine receptors. Zolpidem binding sites are abundant in the basal ganglia output structure the globus pallidus interna and substantia nigra pars reticulata. It is thought that by binding to these sites, zolpidem help restore Ie ganglionic output influence to the thalamus and motor cortex. CONCLUSION: There are several options to treat dystonia,its medical treatment is notoriously difficult and often unsuccessful. Zolpidem an imidazopyridine agonist can be given in childhood dystonia unresponsive to dopamine.

A Randomized, double-blind, placebo-controlled study comparing the efficacy, safety and tolerability of levodopa-carbidopa versus placebo in patients with X-linked dystonia-parkinsonism (XDP)

BACKGROUND: XDP is an X-linked recessive disorder characterized by parkinsonism and dystonia described among Filipinos. Oral medications are frequently ineffective. Lately, DBS have been promising. However these are not generally available or affordable for the vast majority of patients. We then decided to evaluate the effectiveness of levodopa-carbidopa for XDP. OBJECTIVE: To compare the efficacy, safety and tolerability of levodopa-carbidopa vs. placebo in XDP patients. METHODS: After informed consent and randomization, the BFM and the UPDRS parts III and IV were performed at baseline and monthly up to 6 months. Patients were randomized to receive either levodopa-carbidopa at a starting dose of 125 mg levodopa/ day in 2 divided doses or corresponding placebo. Gradual uptitration was done to a maximum of 1000 mg levodopa/ day or until side effects appeared. Homogeneity of the characteristics of patients in the 2 groups was determined using Independent t-test and Chi-square test. To determine the significance of changes in the efficacy parameters within each group, Wilcoxon Matched Pairs Signed Ranks Test was used. To compare the scores of the different efficacy parameters of the 2 groups, Mann Whitney U Test was applied to the data. A p?0.050 was considered significant.RESULTS: A total of 107 patients were recruited. There were 13 screen failures, and 94 were subsequently enrolled. The baseline characteristics (age, duration of illness, baseline BFM and UPDRS (motor) scores were not significant between levodopa and placebo (age in years: 47 + 9.35 vs. 50 + 9.51; duration of illness in years 6.3 + 7 vs. 6.2 + 5.2; BFM score: 32.8 + 24.5 vs. 28.4 + 26.5; UPDRS score 29.9 + 20.7 vs. 34.8 + 26.8). There was a decrease in BFM scores from baseline to all follow-up periods in patients given levodopa but were statistically significant only on visit 2 and visit 9. In the placebo group, decrease in scores was also observed in some observation periods but no statistical significance was shown. A comparison of the 2 groups showed that the magnitude of decrease in the levodopa group was statistically greater than the placebo group on the second visit. There were no significant differences observed in all other follow-up periods. Both groups showed a decrease in UPDRS scores but significant decrease was observed in visits 2, 5, 6, 7, 9 of the levodopa group. While in the placebo group, a significant decrease was observed only on visit 2. Comparison of the 2 groups did not show any significant differences. There were 17 patients from the levodopa group who reported adverse events (most common: increased involuntary movements, nausea/ vomiting/ dizziness, headache, and generalized weakness. In the placebo group, there were 11 patients (most common: increased involuntary movements, abdominal pain). There were 9 patients who dropped out (levodopa: 4, placebo: 5). CONCLUSION: There was a significant decrease in the BFM and UPDRS scores in XDP patients given levodopa compared to placebo. Levodopa is a safe and effective drug that may be considered in patients with XDP. NOTE: This study was supported by an unrestricted grant by Torrent Pharma Philippines, Inc.

Lees' syndrome: a case series / Síndrome de Lees: uma série de casos

We report a case series of dopamine dysregulation syndrome, previously known as hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies, now designated as Lees' syndrome.

Relatamos uma série de casos da síndrome de desregulação dopaminérgica, previamente conhecida como desregulação homeostática hedonística em pacientes com doença de Parkinson em uso de terapia de reposição dopaminérgica, e agora definida como síndrome de Lees.

Two Filipino patients with 6-pyruvoyltetrahydropterin synthase deficiency

Hyperphenylalaninemia can result from defects in either the phenylalanine hydroxylase (PAH) enzyme or in the synthesis or recycling of the active pterin, tetrahydrobiopterin (BH4), which is an obligate co-factor for the PAH enzyme, as well as tyrosine hydroxylase and tryptophan hydroxylase. One of the most common causes of BH4 deficiency is a defect in the synthesis of 6-pyruvoyltetrahydropterin synthase (PTPS) enzyme. Patients present with progressive neurological disease such as mental retardation, convulsions and disturbance of tone and posture despite strict adherence to diet and good metabolic control. The authors report the first two cases of PTPS deficiency in the Philippines. Both are females with initial phenylalanine levels of more than 1300 umol/L who continued to develop neurologic deterioration despite good metabolic control and strict adherence to diet. Further investigation showed that they both had PTPS deficiency. Treatment was started with BH4, L-dopa/carbidopa, and 5-hydroxytryptophan (5HT) with concomitant significant improvements in their neurologic and developmental outcomes.

effect of agents acting on NMDA and dopamine receptors on the responses of phrenic nerve-diaphram preparations from aged rats

Alzheimer's Dementia [AD] and Parkinsonism are common in geriatric patients. The skeletal muscles are important in the proper function of aging animals and humans. This study focuses on the influence of memantine [used for moderate to severe AD] and levodopalcarbidopa [LDICD] [a corner stone in the treatment of Parkinsonism] on responses of isolated phrenic nerve-diaphragms [IPNDs] of aged male rats. From 100 aged male albino rats twenty were untreated to study in vitro effects of memantine and LD/CD on 1PNDs. Eighty rats were divided into: Group-I [Control], Group II [oral meman tine, 1 .5mg/KgId], Group-Ill, [twice daily intraperitoneal LD/CD, 25/2.5mg/kg], Group-lV [both drugs]. After three weeks of treatment, animals were sacrificed; ten rats from each group were used to harvest IPNDs to study the effect of alIamine; 10 rats were used to measure nAchR [nicotinic acetyicholine receptor] alpha subunit mRNA by PCR. Heights of indirectly elicited contractions: 63.1 +/- 4, 6. 41.5 +/- 4.5, 70.6 +/- 4.7, 53.9 +/- 3.3mm for Groups I through IV respectively, all differences were statistically significant K0.05]. Memantine treatment caused a leftward shift of sallamine log-concentration-response curve, LD/CD caused ri.htward shift. Reversal of neuromuscular block required ier neostigmine concentrations in the memantine group it smaller concentrations in the LD/CD group. In Vitro m.antine inhibited diaphragmatic responses to indirect stam1ation. Values of nAchR alpha subunit mRNA [micro g/dl]: 1 +/- f116 [control], 0.13 +/- 0.11 [memnatine], 2.3 +/- 0.94 [LD/CD], 1.18 +/- 0.71 [both drugs] [p<0.05]. Memnatine inhibits neuromuscular transmission in vitro and with in vivo treatment. LD/CD treatment rtaaces neuiomuscular transmission. Clinical implications a1 further investigation

Comparative Cognitive Effects of Levo-Dopa Plus Carbidopa and Dopamine Agonist as an Initial Therapy of Parkinson's Disease

BACKGROUND: Cognitive impairments are common in patients with Parkinson's disease (PD). However little is known about the cognitive effects of dopaminergic therapy. METHODS: The study was a single-blind prospective study of 21 patients with PD. Each patient had received either levodopa (Sinemet(R), n=8) or dopamine agonist (Requip(R), n=13) during 24 consecutive weeks. Neuropsychological battery, including Korean version of Alzheimer's Disease Assessment Scale(R) cognitive subscale (ADAS-Cog) and frontal-executive function part of SNSB (Seoul Neuropsychological Screening Battery), were performed two times, before and after the 24 weeks of management. Patients also received quantitative ratings of motor symptom severity and functional status using Unified Parkinson's Disease Rating Scale (UPDRS) before and after the dopaminergic therapy. RESULTS: After six months of treatment, motor scale improved in both groups (p0.05). In ADAS-Cog testing, Requip(R) group improved at more categories than Sinemet(R) group but without statistical difference (p>0.05). The results of frontal-executive function test did not differ between the groups, either. CONCLUSIONS: Our study does not provide an evidence that dopaminergic treatment improves cognitive functions in Parkinson's disease. Furthermore, we found no significant difference in the effect on cognition between the two tested drugs and no difference in the results of the above-listed neuropsychological tests between the first and the last visits.

The Effect of Levodopa on Akinetic Mutism in Bilateral Anterior Cerebral Artery Infarction: A case report

Akinetic mutism is a clinical syndrome in which the patient is unable to speak (mutism) or move (akinesia). Various brain lesions can induce akinetic mutism. We attended a 71-year-old woman who presented with akinetic mutism caused by bilateral anterior cerebral artery infarction. The patient improved after the administration of levodopa com-bined with carbidopa, in response to visual and verbal stimuli. Increased verbal output and spontaneous motor activities were also noted. Levodopa may be helpful to the treatment of akinetic mutism.

Spectrophotometric determination of levodopa, carbidopa and alpha-methyldopa

The dopamine derivatives participate in the regulation of a wide variety of physiological functions in human body and in medication life. A sensitive spectrophotometric method is developed for the determination of levodopa [LD], carbidopa [CD] and alpha methyldopa [MD]. It proposed on the bases of metal complex formation of these compounds with copper tetramine then coupling with 4-aminoantipyrine. The optimum conditions [pH, time, ratio and sequence of addition] are established. The method permits the determination of LD, CD and MD as a rectlinear relation in calibration curve over a concentration range 19.72 to 69.02, 13.79 to 63.34 and 31.24 to 98.94 micro g ml -1, respectively. The obtained data of SD [0.174 to 0.59], CV [0.68 to 1.16%] and correlation coefficient [0.995 to 0.999] reflect the reliability, reproducibility and accuracy of this procedure. The method is applicable to the assay of LD and MD in pharmaceutical drugs [Levocare and Aldomet respectively], and the results are in a good agreement with those obtained by the official method. The method was simple, rapid, reproducible and accurate to follow of medication of schizophrenic patient

Spectrophotometric assay of levodopa and alpha-methyldopa in pharmaceutical products and in biological samples of schizophrenic patients using copper complex and tri-iodide reagent

Two simple, rapid and sensitive spectrophotometric methods are proposed for the determination of levodopa [LD] I, and alpha-methyldopa [alpha -MD] II. The first method is based on coupling of 4-aminoantipyrine [4-AAP] with LD and a alpha -MD to give new ligands that react with copper-tetramine complex to give intense colored chelates of ratios [1:1:1, LD or alpha -MD: 4-AAP: copper tetramine]. The colored products are quantified spectrophotometrically at 520 and 545 nm for LD and a alpha -MD, respectively. The optimization of the experimental conditions is described. The method has been used for the determination of 19.72-69.02 and 31.24-98.94 micro g ml[-1] of drugs I and II, respectively. The accuracy of the method is indicated by the values of recovery [100 +/- 0.2%] and the precision is supported by the low standard deviation [SD 0.17-0.22] and relative standard deviation [RSD=0.59-1.54%]. The second method is based on the formation of ion-pair iodinated inner sphere or outer sphere colored complexes between the drug and iodine or tri-iodide negative ions at pH 5 and room temperature [25 +/- 3°C]. This method has been used for the determination of LD within the concentration range 39.44-78.88 micro g ml[-1] with SD=022-0.24 and recovery percent=100 +/- 0.3%. The sensitivity of the two methods is indicated by Sandell factor of 0.014- 0.016 g cm[2]. The results of the two methods are compared with those of the official method. The interference from common drug additives, degradation products and excepients was also studied. The proposed methods were applied successfully to the determination of LD and alpha-MD in dosage forms. The second method was also successfully applied for the analysis of LD and carbidopa [CD] synthetic mixture of concentration of these drugs similar to that of Aldomost drug form of LD, and also the determination of these drugs in urine of some schizophrenic patients with good precision and accuracy. The reliability of the methods was established by parallel determinations against the official British pharmacopoeia method

Comparación farmacocinética de Sinemet y Grifoparkin (levodopa/carbidopa 250/25 mg) en pacientes con enfermedad de Parkinson avanzada: un estudio con dosis única / Pharmacokinetic comparison of Sinemet and Grifoparkin (levodopa/carbidopa 250/25 mg) in Parkinson s disease: a single dose study

BACKGROUND: There are doubts wether generic medications have the same bioavailability and efficacy compared with the original drugs developed by pharmaceutical companies with research capabilities. AIM: To compare the pharmacokinetics and clinical (motor) responses of Sinemet and Grifoparkin (generic carbidopa/levodopa 250/25 mg) in patients with advanced Parkinson's disease. PATIENTS AND METHODS: Patients were randomly assigned to Sinemet (15 patients 62 +/- 12 years old; mean disease duration 11 +/- 7 years) or Grifoparkin (15 patients, 64 +/- 11 years old; mean disease duration 12 +/- 4 years) groups. Medication and food were withheld 12 h before the study. Fifteen blood samples were collected (starting 9 AM) immediately before (sample 1, t = 0 min) and after (samples 2-15, t = 20-360 min) oral administration of a single dose of Sinemet or Grifoparkin, and plasmatic L-DOPA was quantified using HPLC with electrochemical detection. Additionally, each patient was clinically evaluated every 20 minutes, using the tapping test and the unified Parkinson's disease scale Hoehn & Yarh. RESULTS: Tmax (time at which the maximal L-DOPA concentration was reached) were 69 +/- 12 min and 64 +/- 11 min for Sinemet and Grifoparkin respectively (NS). Cmax (maximal L-DOPA concentration reached) was 3161 +/- 345 ng/ml for Sinemet and 3274 +/- 520 ng/ml for Grifoparkin (NS). The t1/2 (half life time), CL (clearance) and volume of distribution (Vd) values calculated were 159 +/- 32 min, 51.7 +/- 5.1 1/h and 3.6 +/- 1.2 l/kg for Sinemet and 161 +/- 48 min, 58.7 +/- 8 l/h and 3.0 +/- 0.7 l/kg for Grifoparkin (NS). UPDRS-III value for the best on state and for the worst off state were 23 +/- 11 and 50 +/- 19 for Sinemet and 20 +/- 7 and 46 +/- 13 for Grifoparkin respectively (NS). CONCLUSION: The results obtained showed that both drugs are bioequivalent in patients with advanced Parkinson's disease.

Role of adenosine in drug-induced catatonia in mice.

Parkinson's disease is one of the most common neurodegenerative disorders affecting large majority of population who are older than age of 65. Apart from dopamine, acetylcholine and glutamate, adenosinc has also been identified in the basal ganglia. Adenosine modulates the release of a variety of neurotransmitters including dopamine. In order to establish adenosine-dopamine interactions in drug-induced catatonia we studied the effect of adenosine in drug-induced catatonia in mice. In the present study adenosine dose dependently produced catatonia when assessed on rota-rod and bar tests in mice. Adenosine also potentiated the catatonic effect of perphenazine. L-dopa plus carbidopa or OR-486 (a potent centrally acting COMT inhibitor) completely reversed adenosine-induced catatonia. Since reversal by scopolamine of adenosine-induced catatonia was not to the same extent as with l-dopa and OR-486 it appears that catecholamines particularly dopamine rather than cholinergic modulation is more important in adenosine induced catatonia. The motor dysfunction (catatonia) could be easily assessed using rota-rod test apparatus in mice.

Periodic limb movement disorder : a clinical and polysomnographic study.

Periodic limb movement disorder (PLMD) is one of the commonest neurological disorders and causes significant disability, if left untreated. However, it is rarely diagnosed in clinical practice, probably due to lack of awareness and/or lack of necessary diagnostic facilities. Restless leg syndrome (RLS), aging, pregnancy, uraemia, iron deficiency, polyneuropathy are some of the common causes of secondary PLMD. Clinical presentation, polysomnographic findings and management of six patients of PLMD have been discussed in this report.