- One-pot Synthesis of Indole-3-Acetic Acid Derivatives through Cascade Tsuji-Trost Reaction and Heck Coupling. [Journal Article]
- JOJ Org Chem 2018 May 15
- A practical palladium-mediated cascade Tsuji-Trost reaction/Heck coupling of N-Ts o-bromoanilines with 4-acetoxy-2-butenonic acid derivatives using a Pd(OAc)2/P(o-tol)3/DIPEA system is described for ...
A practical palladium-mediated cascade Tsuji-Trost reaction/Heck coupling of N-Ts o-bromoanilines with 4-acetoxy-2-butenonic acid derivatives using a Pd(OAc)2/P(o-tol)3/DIPEA system is described for a straightforward synthesis of indole-3-acetic acid derivatives. This methodology was successfully applied to synthesize various substituted indole/azaindole-3-acetic acid derivatives and Almotriptan, which is a drug for the acute treatment of migraine. Moreover, a plausible cyclization mechanism has been proposed.
- Association between industry payments and prescribing costly medications: an observational study using open payments and medicare part D data. [Journal Article]
- BHBMC Health Serv Res 2018 Apr 02; 18(1):236
- CONCLUSIONS: A physician-industry financial relationship was associated with increased odds of prescribing costly brand-name drugs of uncertain medical benefit. Patients, as healthcare consumers, should demand transparency from their physicians about payment from the pharmaceutical industry to increase shared decision-making. Physician and policy makers need increased awareness and reflection on how industry payment influences their prescribing practices.
- Stability-Indicating Reversed-Phase UHPLC Method Development and Characterization of Degradation Products of Almotriptan Maleate by LC-QTOF-MS/MS. [Journal Article]
- JCJ Chromatogr Sci 2018 Jan 01; 56(1):6-17
- Almotriptan maleate (ALMT), a highly selective 5-hydroxy tryptamine 1B/1D (5-HT1B/1D) receptor agonist used in the treatment of migraine headache was subjected to various ICH (Q1A (R2)) specified gui...
Almotriptan maleate (ALMT), a highly selective 5-hydroxy tryptamine 1B/1D (5-HT1B/1D) receptor agonist used in the treatment of migraine headache was subjected to various ICH (Q1A (R2)) specified guidelines. The drug underwent significant degradation under hydrolytic (acid, base and neutral), oxidative and photolytic stress conditions, while it was stable under thermal stress condition. A total of seven significant degradation products (DPs) were obtained. A simple, selective and reliable UPLC method has been developed for the separation of ALMT and its DPs using Acquity UPLC HSS Cyano (100 × 2.1 mm, 1.8 μm) column with mobile phase consisting of ammonium acetate (10 mM, pH 4.4) buffer and acetonitrile in gradient elution mode. Chromatographic analysis was performed at a flow rate of 0.3 mL/min using a PDA detector at a wavelength of 230 nm. All the DPs (DP-1 to DP-7) were characterized using UHPLC-ESI-QTOF based on mass fragmentation pattern and accurate m/z values. The developed UPLC method was validated in terms of specificity, linearity, precision and accuracy. The developed stability-indicating method helps in quantification of drug in the presence of DPs.
- From prescription-only (Rx) to over-the-counter (OTC) status in Germany 2006-2015: pharmacological perspectives on regulatory decisions. [Journal Article]
- EJEur J Clin Pharmacol 2017; 73(7):901-910
- CONCLUSIONS: The stipulations of the EU switch guide were fully met for only some switches, while this was not completely the case for others. Further development of guidance on balancing risks and benefits of OTC availability is recommended.
- P074. Almotriptan in the acute treatment of Vestibular migraine: a retrospective study. [Journal Article]
- JHJ Headache Pain 2015; 16(Suppl 1):A114
- Network meta-analysis of migraine disorder treatment by NSAIDs and triptans. [Meta-Analysis]
- JHJ Headache Pain 2016; 17(1):113
- CONCLUSIONS: This study suggests that eletriptan may be the most suitable therapy for migraine from a comprehensive point of view. In the meantime ibuprofen may also be a good choice for its excellent tolerability. Multi-component medication also attracts attention and may be a promising avenue for the next generation of migraine treatment.
- Menstrual Migraine and Treatment Options: Review. [Review]
- HHeadache 2017; 57(2):194-208
- CONCLUSIONS: MM can be very difficult to treat. For acute treatments, rizatriptan has the best overall evidence. For short-term prevention, frovatriptan, zolmitriptan, or naratriptan, as well as magnesium, estrogen, naproxen sodium, or dihydroergotamine may be useful.
- Spotlight on frovatriptan: a review of its efficacy in the treatment of migraine. [Review]
- DDDrug Des Devel Ther 2016; 10:3225-3236
- Migraine is a common neurovascular disorder, affecting millions of people worldwide. Current guidelines recommend triptans as first-line treatment for moderate-to-severe migraine attacks. Frovatripta...
Migraine is a common neurovascular disorder, affecting millions of people worldwide. Current guidelines recommend triptans as first-line treatment for moderate-to-severe migraine attacks. Frovatriptan is a second-generation triptan with a longer terminal elimination half-life in blood than other triptans (~26 hours). Three double-blind, randomized crossover preference studies have been recently conducted, assessing efficacy and safety of frovatriptan versus rizatriptan, zolmitriptan, and almotriptan, respectively. Frovatriptan showed favorable tolerability and sustained effect, with a significantly lower rate of relapse over 48 hours versus the other triptans. These findings were confirmed in a series of analyses of patient subsets from the three studies, including patients with menstrually related and oral contraceptive-induced migraine, hypertension, obesity, weekend migraine, as well as patients with migraine with aura. In all patient subsets analyzed, lower headache recurrence rates were observed versus the comparator triptans, indicating a more sustained pain-relieving effect on migraine symptoms. A further randomized, double-blind study demonstrated that frovatriptan given in combination with the fast-acting cyclooxygenase inhibitor dexketoprofen provided improved migraine pain-free activity at 2 hours, and gave more sustained pain-free activity at 24 hours, versus frovatriptan alone. These benefits were observed both when the combination was administered early (<1 hour after symptom onset) or late (>1 hour after onset). Different pharmacokinetic, but synergistic, properties between frovatriptan and dexketoprofen may make the combination of these agents particularly effective in migraine treatment, with rapid onset of action and sustained effect over 48 hours. These benefits, together with potential cost-effectiveness advantages versus other triptans could drive selection of the most appropriate treatment for acute migraine attacks.
- Comparative tolerability of treatments for acute migraine: A network meta-analysis. [Review]
- CCephalalgia 2017; 37(10):965-978
- Introduction Migraine headache is a neurological disorder whose attacks are associated with nausea, vomiting, photophobia and phonophobia. Treatments for migraine aim to either prevent attacks before...
Introduction Migraine headache is a neurological disorder whose attacks are associated with nausea, vomiting, photophobia and phonophobia. Treatments for migraine aim to either prevent attacks before they have started or relieve attacks (abort) after onset of symptoms and range from complementary therapies to pharmacological interventions. A number of treatment-related adverse events such as somnolence, fatigue, and chest discomfort have previously been reported in association with triptans. The comparative tolerability of available agents for the abortive treatment of migraine attacks has not yet been systematically reviewed and quantified. Methods We performed a systematic literature review and Bayesian network meta-analysis for comparative tolerability of treatments for migraine. The literature search targeted all randomized controlled trials evaluating oral abortive treatments for acute migraine over a range of available doses in adults. The primary outcomes of interest were any adverse event, treatment-related adverse events, and serious adverse events. Secondary outcomes were fatigue, dizziness, chest discomfort, somnolence, nausea, and vomiting. Results Our search yielded 141 trials covering 15 distinct treatments. Of the triptans, sumatriptan, eletriptan, rizatriptan, zolmitriptan, and the combination treatment of sumatriptan and naproxen were associated with a statistically significant increase in odds of any adverse event or a treatment-related adverse event occurring compared with placebo. Of the non-triptans, only acetaminophen was associated with a statistically significant increase in odds of an adverse event occurring when compared with placebo. Overall, triptans were not associated with increased odds of serious adverse events occurring and the same was the case for non-triptans. For the secondary outcomes, with the exception of vomiting, all triptans except for almotriptan and frovatriptan were significantly associated with increased risk for all outcomes. Almotriptan was significantly associated with an increased risk of vomiting, whereas all other triptans yielded non-significant lower odds compared with placebo. Generally, the non-triptans were not associated with decreased tolerability for the secondary outcomes. Discussion In summary, triptans were associated with higher odds of any adverse event or a treatment-related adverse event occurring when compared to placebo and non-triptans. Non-significant results for non-triptans indicate that these treatments are comparable with one another and placebo regarding tolerability outcomes.
New Search Next
- Newly Approved Agents for the Treatment and Prevention of Pediatric Migraine. [Review]
- CDCNS Drugs 2016; 30(9):837-44
- Treatment of pediatric migraine remains an unmet medical need. There continues to be a paucity of pediatric randomized controlled trials for the treatment of migraine, both in the acute and preventiv...
Treatment of pediatric migraine remains an unmet medical need. There continues to be a paucity of pediatric randomized controlled trials for the treatment of migraine, both in the acute and preventive settings. Pediatric studies are often complicated by high placebo-response rates and much of our current practice is based on adult trials. This lack of significant pediatric studies results in a wide variation in migraine management both amongst clinicians and between institutions, and evidence-based treatments are not always administered. In this article, we aim to briefly review newly approved abortive and preventive agents for migraine in the pediatric age group. Over-the-counter anti-inflammatory medications, including ibuprofen, naproxen sodium, aspirin, and acetaminophen are reasonable first-line options for abortive therapy. In addition, studies have shown triptans, or migraine-specific agents, to be safe and effective in children and adolescents and several formulations have been approved for the pediatric population, including rizatriptan, almotriptan, zolmitriptan nasal spray, and naproxen sodium/sumatriptan in combination.