Ibopamine challenge testing becomes negative following successful trabeculectomy surgery.

BACKGROUND: The ibopamine challenge test correlates well with a patient's peak diurnal intraocular pressure (IOP) measurement. We aimed to investigate the effect that a functioning trabeculectomy has on the ibopamine challenge test. DESIGN: Non-randomized prospective clinical trial evaluating a diagnostic test. PARTICIPANTS: Thirteen patients were recruited through glaucoma clinics at the Flinders Medical Centre. Of these, seven required surgical management with trabeculectomy surgery, whilst the remainder were managed medically. METHODS: Patients underwent IOP measurement, and then two drops of Ibopamine 2% solution were instilled into the study eye of each patient. After 45 min, IOP was reassesed. A positive challenge test was considered to be a rise in IOP of greater than 3 mmHg. Changes from baseline were determined and compared between groups. Twelve months later, this test was then repeated in all patients. MAIN OUTCOME MEASURE: Change in IOP after ibopamine challenge. RESULTS: Following the ibopamine challenge, IOP increased by 9.2 mmHg (SD 2.8) (100% positive) for medically managed patients and 7.2 mmHg (SD 2.0) (100% positive) for surgically managed patients (P = 0.18). The surgically managed group then underwent trabeculectomy surgery. Twelve months later, the ibopamine challenge was repeated. Following the repeat ibopamine challenge, IOP increased by 7.2 mmHg (SD 2.3) for medically managed patients and 0.3 mmHg (SD 1.3) for surgically managed patients (P < 0.0001). The medically managed group remained 100% positive, whilst the surgically manage group became 0% positive (Fisher Exact P = 0.044). CONCLUSIONS: A glaucoma patient with a positive ibopamine challenge will show a negative challenge result when re-tested following trabeculectomy surgery.

Avaliação do comportamento da pressão intraocular em pacientes com glaucoma primário de ângulo aberto assimétrico submetidos ao teste provocativo da ibopamina / Evaluation of the intraocular pressure behavior in patients with assimetric primary open-angle glaucoma submitted to ibopamine provocative test

OBJETIVO: Avaliar o efeito da ibopamina a 2 por cento tópica e comparar a variação na pressão intraocular (PIO) em olhos com glaucoma primário de ângulo aberto assimétrico (GPAA). MÉTODOS: Quinze pacientes (30 olhos) com GPAA com evolução assimétrica da neuropatia entre os dois olhos, onde comparamos em cada paciente a resposta a ibopamina e o defeito perimétrico, caracterizado por uma diferença de pelo menos 5dB de MD entre os olhos. O teste estatístico utilizado foi o t Student bicaudal e para significância estatística estabeleceu-se p <0,05. RESULTADOS: Em 80 por cento dos casos, (12/15 pacientes) o olho mais afetado pelo defeito perimétrico apresentou um aumento da PIO e/ou uma variaçã da PIO pós-ibopamina maior, sendo o resultado estatisticamente significativo (p<0,0001 e p = 0,0006), respectivamente. CONCLUSÃO: Este estudo mostrou que o defeito perimétrico no GPAA é significativamente relacionado com a positividade do teste de ibopamina sendo que olhos com maior defeito no campo visual apresentam maiores picos de PIO (max-PIO) pós-ibopamina e/ou uma maior variação em relação a sua PIO prévia ao teste (v-PIO).

OBJECTIVE: To evaluate the topic 2 percent ibopamine effect in the intraocular pressure (IOP) of eyes with assimetric primary open-angle glaucoma (POAG). METHODS: 15 patients (30 eyes) with primary open-angle glaucoma showing assimetric nerve disease evolution were assessed. We compared in all patients, the ibopamine response and the visual field defect between both eyes. The visual field, to be considered, should have at least 5 dB in MD difference between them. The statistical analysis was done with the Two-Tailed Student Test, with a Statistics significance of p<0.05. RESULTS: In 80 percent of the cases, (12/15 patients), the most affected eye in the visual field presented a greater variation and/or higher intraocular pressure after the ibopamine provocative test. The difference was statistically significant (p<0.00001 and p= 0.0006) respectively. CONCLUSION: This study showed that the visual field defect in GPAA is significantly connected with the positivity of the ibopamine test. The most affected eyes in the visual field presented a higher intraocular pressure (max-PIO) and/or a greater variation (v-PIO) after the ibopamine provocativetest.

Efeitos da ibopamina 2 por cento tópica nos resultados da campimetria visual computadorizada / Effects of 2 percent ibopamine eye drops on computerized visual field results

OBJETIVO: Avaliar os efeitos do uso do colírio de ibopamina a 2 por cento nos resultados da campimetria visual computadorizada em indivíduos normais. MÉTODOS: Voluntários oriundos do CEROF-UFG, sem alterações ao exame oftalmológico que pudessem afetar o campo visual foram selecionados. Os indivíduos foram submetidos a exame de perimetria computadorizada SITA-standard 24-2 antes e após dilatação com o colírio de ibopamina a 2 por cento ou ciclopentolato, com intervalo mínimo de 3 dias entre si e em ordem aleatória. Índices globais e número de pontos alterados foram comparados entre os grupos. RESULTADOS: Foram avaliados 30 olhos de 30 indivíduos normais. Não houve diferença estatisticamente significativa entre o "mean deviation" (MD) nos pacientes não dilatados e nos mesmos após a instilação da ibopamina (MD: -1,05 ± 0,26 dB vs. -1,47 ± 0,20 dB, P=0,08), o que ocorreu após cicloplegia (MD: -3,19 ± 0,29 dB), P<0,001 para ambos. Na avaliação entre cicloplegia e pré-dilatação, nota-se significância para o "pattern standard deviation" (P=0,04), o que não ocorreu na avaliação com ibopamina. O número de pontos alterados no "pattern deviation" não apresentou diferença significativa entre todos os pares. Quanto ao número de pontos do "total deviation", houve diferença estatisticamente significativa antes da dilatação e após o uso do cicloplégico (n: 8,86 ± 1,51 vs. 25,72 ± 2,96 pontos, P<0,001) e entre olhos após a instilação do cicloplégico e da ibopamina (ibopamina: 9,75 ± 1,85 pontos, P<001). CONCLUSÃO: O colírio de ibopamina 2 por cento aparentemente não afeta os resultados da perimetria computadorizada em indivíduos normais.

PURPOSE: To evaluate the influence of 2 percent ibopamine eye drops on the results of computerized visual field exams. METHODS: Normal volunteers from CEROF-UFG were selected, with no variance in the ophthalmologic examination that could affect the visual field test. The volunteers underwent computerized visual field test before and after dilation with 2 percent ibopamine eye drop or cyclopentolate, with a minimum interval of three days between them and in a random order. Global indices and number of altered points were compared between the groups. RESULTS: Thirty eyes of 30 normal individuals were selected. There was no statistically significant difference on Mean Deviation (MD) before and after dilation with ibopamine (MD: -1.05 ± 0.26 dB vs. -1.47 ± 0.20 dB, P=0.08). However, after cycloplegia (MD: -3.19 ± 0.29 dB), there was a significant difference on MD (P<0.001 for both ibopamine and pre-dilation). No significant difference was detected in the Pattern Standard Deviation when comparing ibopamine with pre-dilation and cycloplegia values, but it was statistically significant comparing pre-dilation to cycloplegia (P=0.04). The number of altered points in the Pattern Deviation graphic were not significant comparing all pairs. There was a statistically significant difference in the number of altered points in the total deviation graphic before dilation and after cycloplegia (n: 8.86 ± 1.51 vs. 25.72 ± 2.96 points, P<0.001), and comparing cycloplegia with ibopamine (ibopamine: 9.75 ± 1.85 points, P<0.001). CONCLUSION: Ibopamine 2 percent eye drops seem to not modify the results of visual field tests in normal individuals.

Neurotoxicity mechanisms of thioether ecstasy metabolites.

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy"), is a widely abused, psychoactive recreational drug that is known to induce neurotoxic effects. Human and rat hepatic metabolism of MDMA involves N-demethylation to 3,4-methylenedioxyamphetamine (MDA), which is also a drug of abuse. MDMA and MDA are O-demethylenated to N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA) and alpha-methyldopamine (alpha-MeDA), respectively, which are both catechols that can undergo oxidation to the corresponding ortho-quinones. Ortho-quinones may be conjugated with glutathione (GSH) to form glutathionyl adducts, which can be transported into the brain and metabolized to the correspondent N-acetylcysteine (NAC) adducts. In this study we evaluated the neurotoxicity of nine MDMA metabolites, obtained by synthesis: N-Me-alpha-MeDA, alpha-MeDA and their correspondent GSH and NAC adducts. The studies were conducted in rat cortical neuronal cultures, for a 6 h of exposure period, under normal (36.5 degrees C) and hyperthermic (40 degrees C) conditions. Our findings show that thioether MDMA metabolites are strong neurotoxins, significantly more than their correspondent parent catechols. On the other hand, N-Me-alpha-MeDA and alpha-MeDA are more neurotoxic than MDMA. GSH and NAC conjugates of N-Me-alpha-MeDA and alpha-MeDA induced a concentration dependent delayed neuronal death, accompanied by activation of caspase 3, which occurred earlier in hyperthermic conditions. Furthermore, thioether MDMA metabolites time-dependently increased the production of reactive species, concentration-dependently depleted intracellular GSH and increased protein bound quinones. Finally, thioether MDMA metabolites induced neuronal death and oxidative stress was prevented by NAC, an antioxidant and GSH precursor. This study provides new insights into the neurotoxicity mechanisms of thioether MDMA metabolites and highlights their importance in "ecstasy" neurotoxicity.

Análogos das prostaglandinas diminuem a sensibilidade do teste provocativo da ibopamina no glaucoma / Prostaglandin analogues reduce the ibopamine provocative test specificity in glaucoma

OBJETIVO: Avaliar o desempenho do teste provocativo da ibopamina em pacientes com glaucoma usuários de drogas hipotensoras. MÉTODOS: Pacientes glaucomatosos foram recrutados do Centro de Referência em Oftalmologia (CEROF) da Universidade Federal de Goiás, e suas drogas hipotensoras em uso registradas. Indivíduos normais foram amigos e parentes dos pacientes. A seguir, foram instiladas duas gotas de ibopamina 2 por cento com intervalo de 5 minutos. A pressão intra-ocular (Pio) foi medida previamente, e após 30, 60 e 180 minutos. No nosso estudo, o teste da ibopamina foi considerado positivo quando a pressão intra-ocular excedeu 4 mmHg em pelo menos uma das medidas. RESULTADOS: Cinquenta e oito olhos de 58 indivíduos (38 glaucomatosos e 20 normais) foram incluídos no estudo. O aumento da pressão intra-ocular foi maior nos pacientes com glaucoma aos 30, 60 e 180 minutos (p<0,001 em todas as ocasiões). O aumento da pressão intra-ocular foi estatisticamente maior aos 30 minutos nos indivíduos que não utilizavam análogos das prostaglandinas (p=0,01). A sensibilidade do teste foi de 68 por cento (87 por cento se excluirmos pacientes em uso de análogos das prostaglandinas), e a especificidade de 95 por cento. CONCLUSÃO: O teste provocativo da ibopamina 2 por cento pode ser ferramenta auxiliar no diagnóstico do glaucoma. Apesar da pequena amostra estudada, sugere-se que olhos em uso de análogos das prostaglandinas têm reduzido a sensibilidade do mesmo.

Topical ibopamine in the treatment of chronic ocular hypotony attributable to vitreoretinal surgery, uveitis, or penetrating trauma.

PURPOSE: To study whether topical ibopamine effectively increases the intraocular pressure in patients with ocular hypotony after vitreoretinal surgery, uveitis, or penetrating trauma. DESIGN: A prospective randomized, double-blind, placebo controlled, crossover study. METHODS: In ten patients with ocular hypotony, an ibopamine 2% solution or placebo eyedrop was administered at 8 am and frequent applanation tonometry was performed during 10 hours on 2 days, 2 weeks apart. RESULTS: The mean IOP integral after administration of ibopamine was 2.4 mm Hg higher (95% CI for median difference in AUC over 480 minutes [P = .010]) compared with placebo. CONCLUSIONS: The results of the study show that an ibopamine 2% eyedrop twice a day may increase the IOP for a period of over 8 hours in patients with hypotony.

Effects of intracerebroventricular administration of 5-(glutathion-S-yl)-alpha-methyldopamine on brain dopamine, serotonin, and norepinephrine concentrations in male Sprague-Dawley rats.

alpha-Methyldopamine (alpha-MeDA) is a metabolite of the serotonergic neurotoxicants 3,4-(+/-)-(methylenedioxy)amphetamine (MDA) and 3,4-(+/-)-(methylenedioxy)methamphetamine (MDMA). alpha-MeDA readily oxidizes, and in the presence of glutathione (GSH) it forms 5-(glutathion-S-yl)-alpha-methyldopamine [5-(glutathion-S-yl)-alpha-MeDA]. Since GSH conjugates of many polyphenols are biologically (re)active, we investigated the role of 5-(glutathion-S-yl)-alpha-MeDA in the acute and long-term neurochemical changes observed after administration of MDA. Intracerebroventricular (icv) administration of 5-(glutathion-S-yl)-alpha-MeDA (720 nmol) to male Sprague-Dawley rats produced behavioral changes similar to those reported after subcutaneous administration of MDA. Thus, animals became hyperactive and aggressive and displayed forepaw treading and Straub tails, behaviors usually seen after administration of serotonin (5-HT) releasers, and consistent with a role for 5-(glutathion-S-yl)-alpha-MeDA in some of the behavioral alterations seen after administration of MDA and MDMA. In addition to the behavioral changes, 5-(glutathion-S-yl)-alpha-MeDA also caused short-term alterations in the dopaminergic, serotonergic, and noradrenergic systems. An increase in dopamine synthesis appears to be a prerequisite for the long-term depletion of brain 5-HT following MDMA administration. However, although 5-(glutathion-S-yl)-alpha-MeDA reproduced some of the effects of MDA on the dopaminergic system and was capable of causing acute increases in 5-HT turnover, a single icv injection of 5-(glutathion-S-yl)-alpha-MeDA did not result in long-term serotonergic toxicity. Thus, although acute stimulation of dopamine turnover may be necessary for long-term serotonergic toxicity, such changes are not sufficient to produce these effects. The effects of a multiple dosing schedule of 5-(glutathion-S-yl)-alpha-MeDA will therefore require investigation before we can define a role for this metabolite in MDA and MDMA mediated neurotoxicity. MDA also produces a pressor response that is related to its ability to release neuronal norepinephrine stores, and 5-(glutathion-S-yl)-alpha-MeDA caused comparable depletions of brain norepinephrine concentrations, indicating that both compounds produce similar effects on the noradrenergic system.

Topical ibopamine and corticosteroids in the treatment of post-surgery ocular hypotony.

PURPOSE: The aim of the present preliminary study, performed on post-surgical hypotony, was the evaluation of the effects on ocular hypotony of the concomitant administration of ibopamine and corticosteroids. METHODS: 14 patients (11 males-3 females; mean age 47 years) with ocular hypotony following several vitroretinal surgical intervention in different districts, were enrolled. The inclusion criteria were: mean IOP during tonometric curve equal or lower than 6 mmHg, stable IOP for at least 60 days, ongoing treatment with 0.1% dexamethasone (4 times/day), successful surgical intervention, 2% ibopamine (4 times/day) was added to the corticosteroid therapy for 30-60 days. RESULTS: Before ibopamine administration, mean IOP was 4.07 mmHg SD 1.71. At the end of the treatment period, mean IOP increased by 89% in comparison to baseline values (+ 3.64 mmHg SD 5.57). This difference was statistically significant (paired t = 2.39; P = 0.03). One month after ibopamine-treatment discontinuation, mean IOP decreased to pre-treatment values (4.86 mmHg SD 3.50). CONCLUSIONS: The results of the present study, although preliminary, suggest the possibility of a future pharmacological treatment of ocular hypotony with ibopamine, whose rationale is based on the increase of aqueous humor production by stimulating the D1 dopaminergic receptor.

Ibopamine: a new preoperative mydriatic for cataract surgery.

Ibopamine is a dopaminergic mydriatic of proven use for fundoscopy. This double-blind prospective trial assessed its efficacy and safety as a preoperative mydriatic agent. 105 patients undergoing extracapsular cataract surgery were randomly allocated to receive Ibopamine 1%, Ibopamine 1% with Cyclopentolate 1%, or the control Phenylephrine 10% with Cyclopentolate 1%. Ibopamine alone achieved good mydriasis prior to anaesthesia, but this was not maintained intraoperatively. Cyclopentolate combined with Ibopamine, produced consistently greater mydriasis than when combined with Phenylephrine, but the difference became less marked as surgery continued. Analysis in relation to the stage of surgery showed that the greatest stimulus to miosis occurred during expression of the nucleus. Pulse rate and blood pressure in the 51 local anaesthetic cases showed no significant difference between the treatment groups, and there was no significant variation from baseline. The incidence of local side effects was similar in the three groups, and there were no systemic symptoms attributable to the drops. In conclusion, Ibopamine is a safe and effective mydriatic agent for cataract surgery, when used in combination with Cyclopentolate.

Reduced disease in aged rats treated chronically with ibopamine, a catecholaminergic drug.

As part of preclinical safety testing for carcinogenicity, postpubertal (50 days old) rats were dosed (0, 30, 90 or 180 mg/kg/day) with ibopamine (N-methyldopamine, 0,0'-diisobutyroyl ester.HCl; SK&F 100168) for 730 consecutive days. Neoplastic and nonneoplastic lesions were identified histologically in all rats that died during the period of dosing, as well as in those that were killed after it was completed. Six neoplastic lesions (adrenal cortical, mammary, and pituitary adenoma, skin papilloma, pheochromocytoma and mammary adenocarcinoma) and five nonneoplastic lesions (chronic glomerulonephropathy, renal pelvic mineralization, hepatocellular proliferative nodule, galactoceles and chronic cardiomyopathy) were significantly reduced in a dose-related fashion in at least one sex of ibopamine-treated rats. In addition, age-related alopecia and atrophy of the adrenal zona glomerulosa were retarded by ibopamine treatment. Squamous cell skin carcinoma was the only lesion that was significantly (p less than 0.05) increased in the treated groups. Mortality during the study was not significantly different in treated and control groups, indicating that the lower incidence of disease in ibopamine-treated rats was a drug effect and not an artifact of differential survival. Although life span was not measured, ibopamine-treated rats had significantly less malignant lesions than controls at the end of dosing, suggesting a potentially positive effect of treatment on population survival. As the result of these beneficial effects, ibopamine may be useful for future study of factors affecting the occurrence of disease during aging.