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Pharmacological Activity of Pyrazole Derivatives as an Anticonvulsant for Benefit against Epilepsy

Gao M, Qu K, Zhang W, Wang X

Neuroimmunomodulation, 2021;28(2):90-98.
PMID: 33774633 DOI: 10.1159/000513297

INTRODUCTION: Pediatric patients with epilepsy are prone to cognitive impairments during growth and long-term use of most antiepileptic drugs (AED). The affected children do not respond to conventional AED and may require novel drugs to manage the disease. Valproic acid, a first-line drug to treat epilepsy, is associated with serious side effects, which precludes its wider use. Thus, in the present study, we intended to develop novel substituted pyrazoles.
METHODS: The molecules were tested for anticonvulsive activity in Swiss albino mice via maximal electroshock seizure and subcutaneous pentylenetetrazole assays. The most potent molecule among the class was further assayed for its effect on behavioral and CNS depressant activity. The effect of the most potent compounds was also analyzed on various indices of oxidative stress and inflammation in mice.
RESULTS: The designed compounds showed significant anticonvulsive activity in mice revealing 7h as the most potent anticonvulsive agent. The most potent anticonvulsant molecule 7h further showed no behavioral alteration and considerable CNS depressant activity. It also reduces the level of oxidative stress and inflammation in the mice.
CONCLUSION: Our study demonstrated utility of pyrazole derivatives as anticonvulsants against epilepsy.

Matched MeSH terms: Pyrazoles/therapeutic use
Fulltext Endocannabinoid system and cardio-metabolic risk

Loh KY, Kew ST

Med J Malaysia, 2008 Oct;63(4):348-50; quiz 351.
PMID: 19385504 MyJurnal

Recent research in bio-medical science has shown an integral role of endocannabinoid system (ECS) in determining cardio-metabolic risk of human body. The mechanism is mediated through binding of endocannabinoids at the CB1 receptors. The stimulation of CB1 receptor in the brain is believed to control and mediate the effects on appetite. In normal physiology, CB1 receptors activation is responsible for energy homeostasis, govern emotions and behaviors such as anxiety, fear, appetite, food and water intake. CB1 receptors also found in peripheral tissues like liver, pancreas, skeletal muscles and adipose tissues, which play an important role in lipid and glucose metabolism. Over-activation of ECS is associated with various metabolic diseases such as dyslipidemia, insulin resistance, lipogenesis, excessive weight gain and increasing intra-abdominal obesity. All these events lead to increased cardiovascular risk. Use of selective CB1 receptor blocker such as rimonabant has shown to reduced waist circumference, better glycemic control, lower triglyceride levels, raise HDL cholesterol and over all reduction in total body fat. This drug has been recommended for patients with metabolic syndrome.

Matched MeSH terms: Pyrazoles/therapeutic use
Fulltext Randomised, open label, controlled trial of celecoxib in the treatment of acute migraine

Loo CY, Tan HJ, Teh HS, Raymond AA

Singapore Med J, 2007 Sep;48(9):834-9.
PMID: 17728965

INTRODUCTION: Migraine is a common disabling condition that results in considerable socioeconomic loss. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in acute migraine has been well-established. We compared the efficacy of the cyclooxygenase-2 inhibitor celecoxib with the NSAID, naproxen sodium, in the treatment of acute migraine.
METHODS: This was a randomised, open label, controlled trial. We selected patients with a diagnosis of migraine, based on the International Headache Society revised criteria. 60 patients were randomised to either celecoxib 400 mg (30 patients) or naproxen sodium 550 mg (30 patients). Patients took the study medicine for the first acute migraine episode that occurred during the study period and reported the headache reduction based on a visual analogue score (VAS). Patients were reviewed after a month to check on VAS at one and two hours, compared to the baseline. Any side effects of the medication were also recorded.
RESULTS: Of the 52 patients who completed the study, eight did not experience any headaches. The mean VAS in the celecoxib group improved significantly from baseline (6.48 +/- 1.53) to one hour (4.28 +/- 2.11) and two hours (2.24 +/- 2.57) (p-value is less than 0.0005). The mean VAS in the naproxen sodium group also improved significantly from baseline (7.30 +/- 1.66) to one hour (4.81 +/- 2.50) and two hours (2.63 +/- 2.65) (p-value is less than 0.0005). However, there was no significant difference between the magnitudes of improvement between the treatment groups. The incidence of gastric pain was significantly higher in the naproxen sodium group (p-value is equal to 0.029).
CONCLUSION: In comparison with naproxen sodium, celecoxib was equally effective in relieving pain in acute migraine and caused significantly less gastric pain.

Study site: neurology outpatient clinic in Pusat Perubatan
Universiti Kebangsaan Malaysia (PPUKM)

Matched MeSH terms: Pyrazoles/therapeutic use*
Fulltext Efficacy and tolerability of celecoxib compared with diclofenac slow release in the treatment of acute ankle sprain in an Asian population

Nadarajah A, Abrahan L, Lau FL, Hwang LJ, Fakir-Bolte C

Singapore Med J, 2006 Jun;47(6):534-42.
PMID: 16752024

INTRODUCTION: Cyclooxygenase (COX)-2 selective inhibitors are attractive candidates for treatment of ankle sprain because of their efficacy as anti-inflammatory and analgesic agents and their overall safety, including lack of effect on platelet aggregation. The objective of this study was to assess the efficacy and tolerability of celecoxib compared with diclofenac slow release (SR) in the treatment of acute ankle sprain in an Asian population.
METHODS: In this seven-day, multicentre, double-blind, randomised, parallel-group trial, 370 patients with first- or second-degree ankle sprain occurring at or less than 48 hours prior to the first dose of study medication were randomised to receive celecoxib 200 mg bid (189 patients) after a 400 mg loading dose or diclofenac SR 75 mg bid (181 patients). Patients were required to demonstrate moderate to severe ankle pain on weight bearing (45 mm or greater on a 100 mm visual analogue scale [VAS]) at baseline. The primary efficacy end point was the patient's assessment of ankle pain (VAS on full weight bearing) on day 4.
RESULTS: Celecoxib was as effective as diclofenac SR in improving the signs and symptoms of ankle sprain. At day 4, mean VAS scores for celecoxib and diclofenac SR had decreased to 28 mm and 30 mm, respectively. Treatment differences were not statistically significant. Incidence of upper gastrointestinal adverse events was low in both treatment groups (0.5 percent versus 2.2 percent for celecoxib and diclofenac SR, respectively).
CONCLUSION: Celecoxib, a COX-2 selective inhibitor, is as effective as diclofenac SR in treating ankle sprains. With its platelet-sparing properties, celecoxib may offer an advantage over diclofenac SR in managing musculoskeletal injuries.

Matched MeSH terms: Pyrazoles/therapeutic use*
Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis

Shahnaz Syed Abd Kadir S, Christopeit M, Wulf G, Wagner E, Bornhauser M, Schroeder T, et al.

Eur J Haematol, 2018 Sep;101(3):305-317.
PMID: 29791053 DOI: 10.1111/ejh.13099

INTRODUCTION: Ruxolitinib is the first approved drug for treatment of myelofibrosis, but its impact of outcome after allogeneic stem cell transplantation (ASCT) is unknown.
PATIENTS AND METHODS: We reported on 159 myelofibrosis patients (pts) with a median age of 59 years (r: 28-74) who received reduced intensity ASCT between 2000 and 2015 in eight German centers from related (n = 23), matched (n = 86) or mismatched (n = 50) unrelated donors. Forty-six (29%) patients received ruxolitinib at any time point prior to ASCT. The median daily dose of ruxolitinib was 30 mg (range 10-40 mg) and the median duration of treatment was 4.9 months (range 0.4-39.1 months).
RESULTS: Primary graft failure was seen in 2 pts (4%) in the ruxolitinib and 3 (2%) in the non-ruxolitinib group. Engraftment and incidence of acute GVHD grade II to IV and III/IV did not differ between groups (37% vs 39% and 19% vs 28%, respectively), nor did the non-relapse mortality at 2 years (23% vs 23%). A trend for lower risk of relapse was seen in the ruxolitinib group (9% vs 17%, P = .2), resulting in a similar 2 year DFS and OS (68% vs 60% and 73% vs 70%, respectively). No difference in any outcome variable could be seen between ruxolitinib responders and those who failed or lost response to ruxolitinib.
CONCLUSIONS: These results suggest that ruxolitinib pretreatment in myelofibrosis patient does not negatively influence outcome after allogeneic stem cell transplantation.
Study site: 8 health clinics in Germany

Matched MeSH terms: Pyrazoles/therapeutic use*
Profile of Patients Diagnosed With Acute Venous Thromboembolism in Routine Clinical Practice: The RE-COVERY DVT/PE™ Study

Goldhaber SZ, Ageno W, Casella IB, Chee KH, Schellong S, Singer DE, et al.

Am J Med, 2020 08;133(8):936-945.
PMID: 32325043 DOI: 10.1016/j.amjmed.2020.03.036

BACKGROUND: The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions.
METHODS: In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later.
RESULTS: A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke.
CONCLUSIONS: These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice.

Matched MeSH terms: Pyrazoles/therapeutic use