Effects Of Topiramate Research Articles

Topical Topiramate Improves Wound Healing in an Animal Model of Hyperglycemia.

Wound healing is severely affected in hyperglycemia and other metabolic conditions. Finding new therapeutic approaches that accelerate wound healing and improve the quality of the scar may reduce the morbidity commonly associated with skin lesions in diabetes. This study evaluated the effect of topical topiramate (TPM) on wound healing in C57 mice. Streptozotocin-induced hyperglycemic mice were subjected to a wound on the back and randomly allocated for treatment with either vehicle or topical TPM cream (2%) once a day for 14 days. Polymerase chain reaction, Western blotting, and microscopy were performed for the analysis. TPM improved wound healing (complete resolution at Day 10, 98% ± 5 for TPM vs. 81% ± 28 for vehicle), increased organization and deposition of collagen Type I, and enhanced the quality of the scars as determined by microscopy. In addition, TPM modulated the expression of cytokines and proteins of the insulin-signaling pathway: In early wound-healing stages, expression of interleukin-10, an anti-inflammatory marker, increased, whereas at the late phase, the pro-inflammatory markers tumor necrosis factor-α and monocyte chemoattractant protein-1 increased and there was increased expression of a vascular endothelial growth factor. Proteins of the insulin-signaling pathway were stimulated in the late wound-healing phase. Topical TPM improves the quality of wound healing in an animal model of hyperglycemia. The effect of TPM is accompanied by modulation of inflammatory and growth factors and proteins of the insulin-signaling pathway. Therefore, topical TPM presents as a potential therapeutic agent in skin wounds in patients with hyperglycemia.

Adverse effects of topiramate in patients with epilepsy in a tertiary care hospital: observational study

Background: Epilepsy is a common chronic neurological disorder characterized by paroxysmal cerebral dysrhythmia. Conventional antiepileptic drugs such as Phenytoin, carbamazepine, phenobarbitone and sodium valproate, have been proven to have good therapeutic effects. There are currently more than 10 different adjuvants which are approved for use in epileptics. Topiramate, a second-generation antiepileptic drug, is being used for several types of partial-onset and generalized-onset seizures. Effective treatment of epilepsy depends on medication compliance. The incidence of adverse effects is an important issue when antiepileptic drugs are prescribed to treat epilepsy. This study was done in Department of Neurology to observe the adverse effects of Topiramate in patients with epilepsy in a Tertiary care hospital.Methods: For this study 100 patients receiving topiramate as an adjuvant drug along with regular anti epileptic drugs were enrolled in the study for prescheduled three months. Data of the patients were collected.Results: In this study we observed that paresthesia (31%) was the commonly noted adverse effect followed by cognitive impairment (24%), sleepiness (19%), nausea (13%), anorexia (9%) and weight loss (4%).Conclusions: Topiramate is a potent antiepileptic drug effective against most seizure types and has relatively favourable pharmacokinetic profile. It is appropriate for initial monotherapy as well as for adjuvant therapy in refractory patients. The major problem limiting its use is the frequent occurrence of cognitive adverse effects, especially expressive language dysfunction, which are reversible upon discontinuation of the medication.

Evaluation of the pharmacological involvement of ATP-sensitive potassium (KATP) channels in the antidepressant-like effects of topiramate on mice.

Acute doses of topiramate (TPM) have been shown to reduce immobility time in the mice forced swimming test (FST) through inhibition of the nitric oxide (NO) pathway. Adenosine triphosphate-sensitive potassium (KATP) channels are known to have an active role in depression. This study investigates the potential participation of KATP channels in the antidepressant-like effect of TPM through the stimulatory effects of NO. FST and tail suspension tests (TST) were applied to adult male mice for assessment of the antidepressant-like activity of TPM. Different doses of glibenclamide and cromakalim were also applied in order to investigate the involvement of KATP channels. Fluoxetine was used as a positive control for evaluation of antidepressant-like effects. In addition, each animal's locomotor activity was evaluated by the open-field test (OFT). TPM (30mg/kg intraperitoneal (i.p.)) had a significant reductive effect on the immobility behavior similar to fluoxetine (20mg/kg). Co-administration of sub-effective doses of glibenclamide (1mg/kg i.p.) and TPM (10mg/kg i.p.) led to significant synergistic effects in FST and TST. Additionally, the results showed that administration of the sub-effective dose of cromakalim (0.1 and 0.3mg/kg i.p.) blocked the antidepressant-like effects of TPM (30mg/kg i.p.) in both tests. These interventions had no impact on the locomotor movement of mice in OFT. This study shows that the antidepressant-like activity of TPM may potentially be mediated by the blocking of the KATP channels.

Acute narrow-angle glaucoma induced by topiramate with acute myopia and macular striae: A case report

We report the case of a 29-year-old epileptic woman who had been on treatment with topiramate 25mg/day for 9 days. She was referred to the Emergency Department due to reduction in far visual acuity (VA) after increasing the dose to 50mg/day two days before. The ocular examination showed bilateral acute angle closure glaucoma (AACG) and macular striae in both eyes (AO) observed by Retinography and Optical Coherence Tomography (OCT). The AACG is a well-known side effect of topiramate, but the macular striae rarely accompanies it. Although macular striae have been previously described in other cases, very few document those using retinography and OCT images. Therefore, it is important to differentiate a case of AACG induced by topiramate from a case of primary AACG, since they differ in their clinical presentation, mechanism of action, and treatment. Mismanagement can have potentially serious consequences.

Effect of Topiramate on Morphine-induced Conditioned Place Preference (CPP) in Rats: Role of ERK and CREB Proteins in Hippocampus and Cerebral Cortex.

In this study, the effect of topiramate, as an antiepileptic drug, was evaluated on morphine craving in rats. The conditioned place preference (CPP) test was used for this purpose. Repeated administration of morphine (10 mg/kg, i.p. for 4 days) induced significant CPP. Administration of topiramate (50 and 100 mg/kg, i.p. for 4 days) with each morphine administration decreased the acquisition of morphine-induced CPP. At the next step, the levels of extracellular signal-regulated kinase (ERK), p-ERK, cAMP responsive element binding (CREB), and p-CREB proteins were evaluated in hippocampus and cerebral cortex using western blot analysis. Following the repeated administration of morphine, the level of p-ERK protein markedly enhanced in both tissues, while topiramate could significantly reduce the phosphorylation of ERK in these brain regions. Additionally, the level of CREB and p-CREB proteins did not change in different groups. Memantine as a positive control reduced the acquisition of morphine-induced CPP. Also, memantine significantly decreased the level of p-ERK protein in hippocampus and cerebral cortex. These results demonstrated that topiramate can attenuate the acquisition of morphine-induced CPP in rats. This effect in part can be mediated through down regulation of p-ERK protein in hippocampus and cerebral cortex.

The effects of topiramate on cognitive functions of patients with focal epilepsy - a follow-up study in a Serbian sample

Introduction/Objective. The aim of this follow-up study was to determine the effects of topiramate therapy on cognitive functions in patients with pharmacoresistant focal epilepsy. Methods. The study sample comprised of 40 topiramate naive patients. The topiramate starting dose was 25 mg, with a fortnightly titration schedule of 25 mg. A wide range of cognitive functions was evaluated through extensive neuropsychological testing at baseline and six months after reaching the target dose (200 mg/day). Results. The most common side effects following the introduction of topiramate were cognitive impairments, reported by 45% of the participants. The neuropsychological scores on attention, executive function, verbal content recall, improved cognitive flexibility, as well as visuospatial ability and speech, obtained at six-month follow-up were significantly lower than at baseline. However, statistically significant correlation between neuropsychological scores and the number of antiepileptic drugs taken alongside topiramate could not be established. Similarly, no statistically significant differences were noted between the percentage of reduced neuropsychological scores at follow-up pertaining to patients with lower and higher baseline cognitive performance. Moreover, regression analysis indicates that the percentage change in the majority of cognitive scores is unrelated to the age at the epilepsy onset, epilepsy duration, presence of brain pathology on magnetic resonance imaging and percentage change in the depression scale score. Conclusion. Despite slow introduction and administration of a relatively small dose, topiramate exhibits adverse effects on a wide range of cognitive functions, which appear unrelated to the number of additional antiepileptic drugs, baseline cognitive functioning, age at the onset of epilepsy and its duration, presence of brain pathology and the extent of depressive symptoms.

Effects of topiramate on the ultrastructure of synaptic endings in the hippocampal CA1 and CA3 sectors in the rat experimental model of febrile seizures: the first electron microscopy report.

The present study aimed at exploring a potentially neuroprotective effect of topiramate (TPM), one of the most commonly used newer-generation, broad-spectrum, antiepileptic drugs against ultrastructural damage of hippocampal synaptic endings in the experimental model of febrile seizures (FS). The study used male young Wistar rats aged 22-30 days, divided into three experimental groups and the control group. Brain maturity in such animals corresponds to that of 1- or 2-year-old children. Hyperthermic stress was evoked by placing animals in a 45°C water bath for four consecutive days. TPM at a dose of 80 mg/kg b.m. was administered with an intragastric tube before and immediately after FS. Specimens (1 mm3) collected from the hippocampal CA1 and CA3 sectors, fixed via transcardial perfusion with a solution of paraformaldehyde and glutaraldehyde, were routinely processed for transmission-electron microscopic analysis. Advanced ultrastructural changes induced by hyperthermic stress were manifested by distinct swelling of hippocampal pre- and post-synaptic axodendritic and axospinal endings, including their vacuolization and disintegration. The axoplasm of the presynaptic boutons contained a markedly decreased number of synaptic vesicles and their abnormal accumulation in the active synaptic region. The synaptic junctions showed a dilated synaptic cleft and a decreased synaptic active zone. TPM used directly after FS was ineffective in the prevention of hyperthermia-induced injury of synaptic endings in hippocampal CA1 and CA3 sectors. However, "prophylactic" administration of TPM, prior to FS induction, demonstrated a neuroprotective effect against synaptic damage in approximately 25% of the synaptic endings in the hippocampal sectors, more frequently located in perivascular zones. It was manifested by smaller oedema of both presynaptic and postsynaptic parts, containing well-preserved mitochondria, increased number and regular distribution of synaptic vesicles within the axoplasm, and increased synaptic active zone. Our current and previous findings suggest that TPM administered "prophylactically", before FS, could exert a favourable effect on some synapses, indirectly, via the vascular factor, i.e. protecting blood-brain barrier components and through better blood supply of the hippocampal CA1 and CA3 sectors, which may have practical implications.

Comparison between baclofen and topiramate in alcohol dependence: A prospective study

Introduction:Baclofen and topiramate are GABAergic drugs, and both have been recommended for the treatment of alcohol dependence as anticraving agent. Several studies have demonstrated the effect of baclofen and topiramate as anticraving, but none has compared them. The main aim of the current study was to assess the baclofen and topiramate as anticraving agent in alcohol dependence during 1 month follow-up.Methodology:After 1-week detoxification protocol, 94 patients were randomly assigned to either baclofen (n = 49) or topiramate (n = 45) for 1-month follow-up. Patients were assessed with clinical institute withdrawal assessment at baseline, and at 1 week, the Addiction Severity Index, ready to change questionnaire at baseline and weekly assessed with Obsessive and Compulsive drinking scale (OCDS) for craving. At every follow-up, adverse effects were also assessed to check tolerability.Results:A marked improvement was observed with baclofen in OCDS in each assessment as compared to topiramate. With baclofen, 61.22% of patients became complete abstinence, as compared to 37.78% in topiramate group. Baclofen was better tolerated as 24.49% patients were dropped out in baclofen group as compared to 33.33% in topiramate group.Conclusion:Baclofen has better efficacy and tolerability as compared to topiramate.

Effects of Chronic Topiramate, Lacosamide, and Levetiracetam Pre-treatment on a Status Epilepticus Model in Rat Pups

We examined possible neuroprotective and prophylactic effects of chronic pre-treatment with levetiracetam (Lev), topiramate (Tpm), and lacosamide (Lcm) on the pentylenetetrazol (PTZ)-induced status epilepticus (SE) in rat pups. Forty-six rats were divided into four groups; all of them were on postnatal day (PD) 21 i.p. injected with 60 mg/kg PTZ. Rat pups of three experimental groups were pre-treated during 14 days (PD7–PD21) with Tpm, Lcm, or Lev via gavage in doses of 60, 50, and 150 mg/kg per day, respectively; animals of the PTZ group were treated with 0.2 ml saline per day. Animals of the latter group demonstrated intense behavioral changes of a stage 3 of the Racine scale or higher, while no significant behavioral alterations were observed in all pre-treated groups. Protein carbonyl and TBARS levels were markedly elevated in the PTZ group, while these indices were significantly smaller in the Tpm and Lev groups. Immunohistochemical analysis demonstrated an increased apoptosis level in hippocampal pyramidal neurons in the Lev group with respect to the PTZ group. In the open field test, the total distance moved and duration of stay in the outer squares were significantly greater in the PTZ group than in the Lcm and Lev groups. Thus, Tpm, Lcm, and Lev treatment provided clear prophylactic effects on the PTZ-induced SE development; such treatment decreased the intensity of oxidative stress and protected from changes in locomotor activity and anxietyrelated behavior in immature organisms. However, some pro-apoptotic action of Lev on the developing hippocampus needs to be noted and investigated in more detail.

Preventive effects of Topiramate on Methylphenidate induced behavioral disorders

Preventive effects of Topiramate on Methylphenidate induced behavioral disorders

Glaucoma agudo de ángulo cerrado inducido por topiramato con miopización aguda y estrías maculares: a propósito de un caso

We report the case of a 29-year-old epileptic woman who had been on treatment with topiramate 25mg/day for 9 days. She was referred to the Emergency Department due to reduction in far visual acuity (VA) after increasing the dose to 50mg/day two days before. The ocular examination showed bilateral acute angle closure glaucoma (AACG) and macular striae in both eyes (AO) observed by Retinography and Optical Coherence Tomography (OCT). The AACG is a well-known side effect of topiramate, but the macular striae rarely accompanies it. Although macular striae have been previously described in other cases, very few document those using retinography and OCT images. Therefore, it is important to differentiate a case of AACG induced by topiramate from a case of primary AACG, since they differ in their clinical presentation, mechanism of action, and treatment. Mismanagement can have potentially serious consequences.

Клинические и нейрофизиологические эффекты топирамата при хронической мигрени

Клинические и нейрофизиологические эффекты топирамата при хронической мигрени

Antimyoclonic Effect of Levetiracetam and Clonazepam Combined Treatment on Myoclonic Epilepsy with Ragged-Red Fiber Syndrome with m.8344A>G Mutation.

Background:Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers (MERRFs) has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects of monotherapies, including levetiracetam (LEV), clonazepam (CZP), valproic acid (VPA), and topiramate (TPM) compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures.Methods:Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1–4 months of follow-up (mean: 82.9 ± 28.1 days), 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The follow-up period was 4–144 months (mean: 66.3 ± 45.3 months), the effective rates of monotherapy group (17 patients) and combination therapy group (12 patients) were analyzed by Chi-square test.Results:The m.8344 A>G mutation was detected in all patients. There were four patients with partial response (4/17, two in the CZP group and two in the LEV group), ten patients with stable disease (10/17, six in the CZP group, three in the LEV group, and one in the TPM group), and three patients with progressive disease (3/18, two in the VPA group and one in the TPM group). Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance (12/12), eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy group in the efficacy of antimyoclonic seizures (χ2 = 13.7, P < 0.001).Conclusions:LEV in combination with CZP is an efficient and safe treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A>G mutation.

Age-Dependent Anti-migraine Effects of Valproic Acid and Topiramate in Rats

Background: Valproic acid (VPA) and topiramate (TPM), initially developed as antiepileptics, are approved for migraine prophylaxis in adults but not children. The differences in their antimigraine mechanism(s) by age remain unclear.Methods: A migraine model induced by intra-cisternal (i.c.) capsaicin instillation in pediatric (4–5 weeks) and adult (8–9 weeks) rats was pretreated with VPA (30, 100 mg/kg) or TPM (10, 30, 100 mg/kg). Noxious meningeal stimulation by the irritant capsaicin triggered trigeminovascular system (TGVS) activation mimicking migraine condition, which were assessed peripherally by the depletion of calcitonin gene-related peptide (CGRP) in sensory nerve fibers of the dura mater, the increased CGRP immunoreactivity at trigeminal ganglia (TG) and centrally by the number of c-Fos-immunoreactive (c-Fos-ir) neurons in the trigeminocervical complex (TCC). Peripherally, CGRP released from dural sensory nerve terminals of TG triggered pain signal transmission in the primary afferent of trigeminal nerve, which in turn caused central sensitization of the TGVS due to TCC activation and hence contributed to migraine.Results: In the VPA-treated group, the central responsiveness expressed by reducing the number of c-Fos-ir neurons, which had been increased by i.c. capsaicin, was significant in pediatric, but not adult, rats. Inversely, VPA was effective in peripheral inhibition of elevated CGRP immunoreactivity in the TG and CGRP depletion in the dura mater of adult, but not pediatric, rats. In TPM group, the central responsiveness was significant in both adult and pediatric groups. Peripherally, TPM significantly inhibited capsaicin-induced CGRP expression of TG in adult, but not pediatric, rats. Interestingly, the capsaicin-induced depletion of CGRP in dura was significantly rescued by TPM at high doses in adults, but at low dose in pediatric group.Conclusion: These results suggest VPA exerted peripheral inhibition in adult, but central suppression in pediatric migraine-rats. In contrast, TPM involves both central and peripheral inhibition of migraine with an optimal therapeutic window in both ages. These findings may clarify the age-dependent anti-migraine mechanism of VPA and TPM, which may guide the development of new pediatric anti-migraine drugs in the future.

Additional sanogenetic effect of topiramate in the treatment of epilepsy in women of childbearing age

A relationship of epilepsy and a used antiepileptic drug (AED) with the menstrual cycle, overweight, and reproductive disorders in women has been studied in recent years. In this connection, topiramate engages attention as one of the AEDs that contribute to weight loss, but not gain.Objective: to investigate the efficacy/tolerability of topiramate in reproductive-aged women with menstrual disorders.Patients and methods. An analysis was made in a group of 58 patients of fertile age (18–35 years) with a long history of focal epilepsy (FE) (n = 44) or idiopathic generalized epilepsy (IGE) (n = 14) who received mainly combined therapy with 2 AEDs. Different degrees of overweight was observed in 82.8% of the patients; 51.7% had one or another menstrual cycle disorders; however, the women had been followed up by a gynecologist in exceptional cases. Switching from one of the parent AEDs to topiramate or its incorporation into a treatment regimen as an additional drug substantially improved the course of the disease: remission at 12 months was achieved in 59.1% of the patients with FE and in 78.6% of those with IGE.Results. 29.3% of the patients receiving dual therapy, the second medication of which was topiramate, were noted to have lost weight not only if those had a high baseline body mass index (BMI), but also if those had normal BMI at baseline. 8.6% of all the patients and 16.7% of those with menstrual cycle disorder achieved normalization of menstrual function. Topiramate was discontinued only in 1 (1.7%) patient because of critical weight loss (BMI&lt;15).Discussion. The use of topiramate that has a wide spectrum of action in different types of seizures and forms of epilepsy in patients with a long history of the disease could achieve seizure remission in 59.1% of the patients with FE and in 78.6% of those with IGE for a period of more than 12 months. One-third of all the cases were observed to have lost 3–13 kg (median, 6 kg) of weight during monotherapy or dual therapy with topiramate. The latter resulted in the normalization of menstrual function in 5 patients, which was 8.6% of all the patients and 16.7% of those with menstrual cycle problems.Conclusion. In addition to a significant improvement in the disease course, the use of topiramate in monotherapy or dual therapy for FE or IGE can contribute to the normalization of body weight and the menstrual cycle. The authors draw the attention of epileptologists to the need to monitor menstrual function in women with epilepsy.

Can the Impact of Topiramate on Memory Processes be Related to Its ‘Antialcoholic Activity’?—A Preclinical Study

Topiramate causes the inhibition of alcohol consumption in addicts but the mechanism of this action has not been fully understood yet. Nowadays, it seems that memory may have a role in the development of dependence. In this study, the impact of topiramate and ethanol on the bioelectric activity of the brain in rabbits and on spatial memory in rats was evaluated. The aim of the study was to assess the effect of co-administration of topiramate and ethanol on bioelectric activity of the rabbits' brain and on spatial memory in rats. Topiramate decreased ethanol-induced changes in all studied brain structures and improved memory and learning processes. A pharmaco-electroencephalography study was used to examine the effect of topiramate (25 mg/kg/day) co-administered for 6 weeks with ethanol on the bioelectric activity of the rabbits' brain. The influence of the drug was also assessed in first and second weeks of the abstinence period. Spatial memory was evaluated in rats using Morris water maze task. Topiramate (60 mg/kg/day) was administered with the ethanol for 3 weeks and for 2 weeks in the abstinence. After 6 weeks of topiramate and ethanol administration, the drug decreased ethanol-induced changes in the midbrain reticular formation, hippocampus and frontal cortex. In the abstinence, the drug also inhibited the features of neuronal hyperactivity, especially in the hippocampus. Moreover, topiramate co-administered with ethanol for 3 weeks decreased ethanol-induced memory disturbance in rats. This beneficial effect was also observed in the second week of abstinence. These findings reveal that 'antialcoholic' activity of topiramate may be associated with its advantageous effect on memory and learning processes.

Chronic and intermittent administration of systemic nitroglycerin in the rat induces an increase in the gene expression of CGRP in central areas: potential contribution to pain processing

BackgroundCalcitonin gene related peptide (CGRP) is a key neuropeptide involved in the activation of the trigeminovascular system and it is likely related to migraine chronification. Here, we investigated the role of CGRP in an animal model that mimics the chronic migraine condition via repeated and intermittent nitroglycerin (NTG) administration. We also evaluated the modulatory effect of topiramate on this experimental paradigm. Male Sprague-Dawley rats were injected with NTG (5 mg/kg, i.p.) or vehicle, every 2 days over a 9-day period (5 total injections). A group of animals was injected with topiramate (30 mg/kg, i.p.) or saline every day for 9 days. Twenty-four hours after the last administration of NTG or vehicle, animals underwent tail flick test and orofacial Von Frey test. Rats were subsequently sacrificed to evaluate c-Fos and CGRP gene expression in medulla-pons region, cervical spinal cord and trigeminal ganglia.ResultsNTG administration induced spinal hyperalgesia and orofacial allodynia, together with a significant increase in the expression of CGRP and c-Fos genes in trigeminal ganglia and central areas. Topiramate treatment prevented NTG-induced changes by reversing NTG-induced hyperalgesia and allodynia, and inhibiting CGRP and c-Fos gene expression in all areas evaluated.ConclusionsThese findings point to the role of CGRP in the processes underlying migraine chronification and suggest a possible interaction with gamma-aminobutyrate (GABA) and glutamate transmission to induce/maintain central sensitization and to contribute to the dysregulation of descending pain system involved in chronic migraine.

Effect of carbamazepine, topiramate and valproate in the treatment of encephalitis secondary epilepsy

目的 比较卡马西平、托吡酯与丙戊酸钠治疗脑炎继发癫痫的临床效果。 方法 选择淳安县第一人民医院2007年1月至2017年1月收治的脑炎继发癫痫患者60例，根据治疗方式的不同将患者分为甲组、乙组和丙组，每组20例，甲组采用卡马西平治疗，乙组采用托吡酯治疗，丙组采用丙戊酸钠治疗，三组均治疗1年。观察三组的临床疗效和不良反应。 结果 甲组、乙组、丙组总有效率分别为70.0%(14/20)、75.0%(15/20)、80.0%(16/20)，三组差异无统计学意义(χ2＝0.763，P＝0.672)。甲组不良反应发生率(37.5%)最高，其次是丙组(22.5%)，乙组不良反应发生率(10.0%)最低，组间差异有统计学意义(χ2＝7.341，P<0.05)。 结论 临床治疗脑炎继发癫痫采用卡马西平、托吡酯及丙戊酸钠均有较佳的效果，但托吡酯的不良反应发生率低，安全性高、耐受性好。

Topiramate is more effective than acetazolamide at lowering intracranial pressure.

BackgroundThe management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats.MethodsWe measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). In addition, we measured intracranial pressure after oral administration of acetazolamide and topiramate.ResultsAt clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% (p = 0.0009) and 21% (p = 0.015) respectively. There was no significant reduction in intracranial pressure noted with acetazolamide, furosemide, amiloride or octreotide at any dose. Oral administration of topiramate significantly lowered intracranial pressure by 22% (p = 0.018), compared to 5% reduction with acetazolamide (p = >0.999).ConclusionOur in vivo studies demonstrated that both subcutaneous and oral administration of topiramate significantly lowers intracranial pressure. Other drugs tested, including acetazolamide, did not significantly reduce intracranial pressure. Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest.

Effects of topical topiramate in wound healing in mice.

Recent studies have indicated that systemic topiramate can induce an improvement on the aesthetic appearance of skin scars. Here, we evaluated topical topiramate as an agent to improve wound healing in C57/BL6 mice. Mice were inflicted with a 6.0mm punch to create two wounds in the skin of the dorsal region. Thereafter, mice were randomly assigned to either vehicle or topical topiramate (20µl of 2% cream) once a day for 14days, beginning on the same day as wound generation. We analyzed the wound samples over real-time PCR, Western blotting, and microscopy. There was no effect of the topiramate treatment on the time for complete reepithelization of the wound. However, on microscopic analysis, topiramate treatment resulted in increased granulation tissue, thicker epidermal repair, and improved deposition of type I collagen fibers. During wound healing, there were increased expressions of anti-inflammatory markers, such as IL-10, TGF-β1, and reduced expression of the active form of JNK. In addition, topiramate treatment increased the expression of active forms of two intermediaries in the insulin-signaling pathway, IRS-1 and Akt. Finally, at the end of the wound-healing process, topiramate treatment resulted in increased expression of SOX-2, a transcription factor that is essential to maintain cell self-renewal of undifferentiated embryonic stem cells. We conclude that topical topiramate can improve the overall quality of wound healing in the healthy skin of mice. This improvement is accompanied by reduced expression of markers involved in inflammation and increased expression of proteins of the insulin-signaling pathway.