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[PMID]:28882644
[Au] Autor:Weon H; Kim TW; Youn DH
[Ad] Endereço:Department of Oral Physiology, BioCure Laboratory, School of Dentistry, Kyungpook National University, 2177 Dalgubeol Blvd, Jung-gu, Daegu 41940, Republic of Korea.
[Ti] Título:Postsynaptic N-type or P/Q-type calcium channels mediate long-term potentiation by group I metabotropic glutamate receptors in the trigeminal oralis.
[So] Source:Life Sci;188:110-117, 2017 Nov 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Both N-type and P/Q-type voltage-gated Ca channels (VGCCs) are involved in the induction of long-term potentiation (LTP), the long-lasting increase of synaptic strength, in the central nervous system. To provide further information on the roles of N-type and P/Q-type VGCCs in the induction of LTP at excitatory synapses of trigeminal primary afferents in the spinal trigeminal subnucleus oralis (Vo), we investigated whether they contribute to the induction of LTP by activation of group I metabotropic glutamate receptors (mGluRs). MAIN METHODS: (S)-3,5-Dihydroxyphenylglycine (DHPG; 10µM for 5min), the group I mGluR agonist, was used to induce LTP of excitatory postsynaptic currents that were evoked in the Vo neurons by stimulating the trigeminal track. KEY FINDINGS: Weak blockade of the N-type or P/Q-type VGCCs by ω-conotoxin GVIA or ω-agatoxin IVA, respectively, which inhibited only 20-40% of Ca currents recorded in isolated trigeminal ganglion neurons but had no effect on the basal excitatory synaptic transmission, completely blocked the induction of LTP. In contrast, stronger blockade of the channels, which inhibited >50% of Ca currents and about 30% of basal synaptic transmission, resulted in the development of long-term depression (LTD), the long-lasting decrease of synaptic strength. Interestingly, the postsynaptic mechanism of DHPG-induced LTP, which was determined by paired-pulse ratio, disappeared when LTP was blocked, or LTD occurred, while a presynaptic mechanism still remained. SIGNIFICANCE: Our data suggest that postsynaptic N-type and P/Q-type VGCCs mediate the DHPG-induced LTP at the trigeminal afferent synapses in the Vo.
[Mh] Termos MeSH primário: Canais de Cálcio Tipo N/fisiologia
Canais de Cálcio Tipo P/fisiologia
Canais de Cálcio Tipo Q/fisiologia
Potenciação de Longa Duração/fisiologia
Receptores de Glutamato Metabotrópico/fisiologia
Núcleo Espinal do Trigêmeo/fisiologia
[Mh] Termos MeSH secundário: Agatoxinas/farmacologia
Animais
Agonistas dos Canais de Cálcio/farmacologia
Bloqueadores dos Canais de Cálcio
Cromonas/farmacologia
Feminino
Potenciação de Longa Duração/efeitos dos fármacos
Depressão Sináptica de Longo Prazo/efeitos dos fármacos
Depressão Sináptica de Longo Prazo/fisiologia
Masculino
Terminações Pré-Sinápticas/fisiologia
Ratos
Receptores de Glutamato Metabotrópico/agonistas
Potenciais Sinápticos/fisiologia
Transmissão Sináptica/efeitos dos fármacos
Núcleo Espinal do Trigêmeo/efeitos dos fármacos
ômega-Conotoxinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((S)-3,7-dihydroxychroman-4-one); 0 (Agatoxins); 0 (Calcium Channel Agonists); 0 (Calcium Channel Blockers); 0 (Calcium Channels, N-Type); 0 (Calcium Channels, P-Type); 0 (Calcium Channels, Q-Type); 0 (Chromones); 0 (Receptors, Metabotropic Glutamate); 0 (omega-Conotoxins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE


  2 / 803 MEDLINE  
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[PMID]:28719378
[Au] Autor:Robert J; Sorrieul J; Rossignol E; Beaussart H; Kieffer H; Folliard C; Dupoiron D; Devys C
[Ad] Endereço:Institute de Cancérologie de l'Ouest Paul Papin, Angers, France.
[Ti] Título:Chemical Stability of Morphine, Ropivacaine, and Ziconotide in Combination for Intrathecal Analgesia.
[So] Source:Int J Pharm Compd;21(4):347-351, 2017 Jul-Aug.
[Is] ISSN:1092-4221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pain is the most feared symptom amongst individuals living with cancer. In 15% to 20% of patients, conventional analgesic therapy either fails to relieve pain or induces adverse effects. Intrathecal drug delivery systems may present an effective alternative for pain management. The Cancerology Center Paul Papin protocol includes an admixture of morphine, ropivacaine, and ziconotide in intrathecal preparations. These drugs are administered by a fully implantable or an external pump. Syringes or polyolefin infusion bags are prepared for refill just before use. Few centers in France use the method of intrathecal analgesia. Therefore, for those patients receiving intrathecal preparations, each filling requires that the patients be transported from their local hospital (or their home) to a referral center where the patients are monitored. They sometimes must travel up to a hundred kilometers to have a pump filled. The preparation and the analytical control of the mixture are carried out only by those centers meeting the proper criteria, which includes the proper equipment. To spare the patient this travel, a peripheral center may be subcontracted to manage the patient's pump refill. No data are available concerning the chemical stability of admixtures in syringes or polyolefin infusion bags. The aim of this study was to evaluate, with a new analytical method using ultra high-performance liquid chromatography, the chemical stability of these admixtures in syringes or in polyolefin infusion bags. Ziconotide 1 µg/mL was combined with ropivacaine (7.5 mg/mL) and morphine (3.5 mg/mL) in syringes at 5°C, 21°C, and 31°C, and in polyolefin infusion bags at 21°C. Assays were performed using ultra high-pressure liquid chromatography. In syringes stored at 21°C and 31°C, concentrations after 6 hours were not in the acceptable criterion of 10% variability. When syringes were stored at 5°C, the residual concentration of ziconotide after 3 days was 100.5% +/- 2.6% [92.7% to 108.4%]. In polyolefin infusion bags, the residual concentration of ziconotide after 14 days was 96.9% +/- 2.2% [90.1% to 103.6%]. This study demonstrates the chemical stability of this admixture in syringes stored at 5°C for 3 days and in polyolefin plastibags stored at 21°C for 14 days.
[Mh] Termos MeSH primário: Amidas/química
Analgésicos/química
Anestésicos Locais/química
Morfina/química
Dor/tratamento farmacológico
ômega-Conotoxinas/química
[Mh] Termos MeSH secundário: Amidas/administração & dosagem
Cromatografia Líquida de Alta Pressão
Combinação de Medicamentos
Estabilidade de Medicamentos
Seres Humanos
Injeções Espinhais
Morfina/administração & dosagem
ômega-Conotoxinas/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Analgesics); 0 (Anesthetics, Local); 0 (Drug Combinations); 0 (omega-Conotoxins); 76I7G6D29C (Morphine); 7I64C51O16 (ziconotide); 7IO5LYA57N (ropivacaine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE


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[PMID]:28330759
[Au] Autor:Chang CY; Hung CF; Huang SK; Kuo JR; Wang SJ
[Ad] Endereço:Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan.
[Ti] Título:Amiodarone reduces depolarization-evoked glutamate release from hippocampual synaptosomes.
[So] Source:J Pharmacol Sci;133(3):168-175, 2017 Mar.
[Is] ISSN:1347-8648
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Decreased brain glutamate level has emerged as a new therapeutic approach for epilepsy. This study investigated the effect and mechanism of amiodarone, an anti-arrhythmic drug with antiepileptic activity, on glutamate release in the rat hippocampus. In a synaptosomal preparation, amiodarone reduced 4-aminopyridine-evoked Ca -dependent glutamate release and cytosolic Ca concentration elevation. Amiodarone did not affect the 4-aminopyridine-evoked depolarization of the synaptosomal membrane potential or the Na channel activator veratridine-evoked glutamate release, indicating that the amiodarone-mediated inhibition of glutamate release is not caused by a decrease in synaptosomal excitability. The inhibitory effect of amiodarone on 4-aminopyridine-evoked glutamate release was markedly decreased in synaptosomes pretreated with the Ca 2.2 (N-type) and Ca 2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, the calmodulin antagonists W7 and calmidazolium, or the protein kinase A inhibitors H89 and KT5720. However, the intracellular Ca -release inhibitors dantrolene and CGP37157 had no effect on the amiodarone-mediated inhibition of glutamate release. Furthermore, amiodarone reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that amiodarone reduces Ca influx through N- and P/Q-type Ca channels, subsequently reducing the Ca -calmodulin/protein kinase A cascade to inhibit the evoked glutamate release from rat hippocampal nerve terminals.
[Mh] Termos MeSH primário: Amiodarona/farmacologia
Antiarrítmicos/farmacologia
Ácido Glutâmico/metabolismo
Hipocampo/efeitos dos fármacos
Sinaptossomos/efeitos dos fármacos
[Mh] Termos MeSH secundário: 4-Aminopiridina/farmacologia
Animais
Ácido Aspártico/farmacologia
Cálcio/fisiologia
Bloqueadores dos Canais de Cálcio/farmacologia
Calmodulina/antagonistas & inibidores
Capsaicina/farmacologia
Carbazóis/farmacologia
Hipocampo/metabolismo
Hipocampo/fisiologia
Imidazóis/farmacologia
Isoquinolinas/farmacologia
Macrolídeos/farmacologia
Masculino
Potenciais da Membrana/efeitos dos fármacos
Inibidores de Proteínas Quinases/farmacologia
Pirróis/farmacologia
Ratos Sprague-Dawley
Sulfonamidas/farmacologia
Sinaptossomos/metabolismo
Sinaptossomos/fisiologia
ômega-Conotoxinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 0 (Calcium Channel Blockers); 0 (Calmodulin); 0 (Carbazoles); 0 (Imidazoles); 0 (Isoquinolines); 0 (Macrolides); 0 (Protein Kinase Inhibitors); 0 (Pyrroles); 0 (Sulfonamides); 0 (benzyloxyaspartate); 0 (omega-Conotoxins); 30KYC7MIAI (Aspartic Acid); 3KX376GY7L (Glutamic Acid); 4R9H38JAWL (calmidazolium); 58HV29I28S (KT 5720); 65595-90-6 (W 7); 88899-55-2 (bafilomycin A1); BH3B64OKL9 (4-Aminopyridine); M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide); N3RQ532IUT (Amiodarone); S07O44R1ZM (Capsaicin); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE


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[PMID]:28195861
[Au] Autor:Patel S; Hafez O; Sexton WJ; Edwards DA
[Ad] Endereço:From the Departments of *Anesthesiology and †Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida; and ‡Department of Anesthesiology, Vanderbilt University, Nashville, Tennessee.
[Ti] Título:Perioperative Management of a Patient With an Intrathecal Drug Delivery Device Infusing Ziconotide: A Case Report.
[So] Source:A A Case Rep;8(4):78-80, 2017 Feb 15.
[Is] ISSN:2325-7237
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Intrathecal ziconotide is used for the treatment of chronic pain and is delivered by an implanted drug delivery device. Anesthesiologists should be familiar with the perioperative management of the pump as well as the potential adverse events related to continued ziconotide infusion during general anesthesia. A case is presented demonstrating the perioperative management of an intrathecal drug delivery device infusing ziconotide in a patient presenting for radical cystectomy with pelvic lymphadenectomy and ileal conduit diversion.
[Mh] Termos MeSH primário: Analgésicos não Entorpecentes/administração & dosagem
Anestesia Geral/métodos
Carcinoma de Células de Transição/cirurgia
Complicações Intraoperatórias/prevenção & controle
Dor Lombar/tratamento farmacológico
Neoplasias da Bexiga Urinária/cirurgia
Vasoplegia/prevenção & controle
ômega-Conotoxinas/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Dor Crônica/tratamento farmacológico
Cistectomia
Desprescrições
Seres Humanos
Bombas de Infusão Implantáveis
Infusão Espinal
Excisão de Linfonodo
Masculino
Pelve
Assistência Perioperatória/métodos
Derivação Urinária
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Non-Narcotic); 0 (omega-Conotoxins); 7I64C51O16 (ziconotide)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170221
[Lr] Data última revisão:
170221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170215
[St] Status:MEDLINE
[do] DOI:10.1213/XAA.0000000000000432


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[PMID]:26861472
[Au] Autor:Brookes ME; Eldabe S; Batterham A
[Ad] Endereço:Department of Anaesthesia and Pain Management, The James Cook University Hospital, Middlesbrough, TS4 3BW, United Kingdom.
[Ti] Título:Ziconotide Monotherapy: A Systematic Review of Randomised Controlled Trials.
[So] Source:Curr Neuropharmacol;15(2):217-231, 2017.
[Is] ISSN:1875-6190
[Cp] País de publicação:United Arab Emirates
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Chronic neuropathic pain is difficult to treat and is often refractory to most modalities of treatment. Ziconotide is a novel, potent, non-opioid, calcium channel blocking agent which has been shown in clinical trials to be effective in treating chronic neuropathic pain. METHODS: EMBASE, MEDLINE, CINAHL Plus and Web of Science electronic databases were searched for English language studies. Reference sections of articles were examined for further papers and the manufacturer of ziconotide was contacted for further unpublished data. Three randomised controlled trials in ziconotide monotherapy were included and subjected to a random effects meta-analysis. RESULTS: All three studies used the similar main outcome measure (visual analogue scale of pain intensity; VASPI) and were therefore comparable. A Jadad score was performed for each paper. Frequent serious adverse events (SAEs) were observed which resulted in two of the studies revising the protocol. The metaanalysis revealed a pooled odds ratio (responders on ziconotide vs. placebo) of 2.77 (95% CI, 1.37 to 5.59). DISCUSSION: The results suggest that ziconotide is beneficial for pain reduction in chronic neuropathic pain. However, there remain some methodological issues that may call into question the validity of the results. It is evident that more work needs to be conducted to further validate the efficacy of ziconotide and to discover new areas of use.
[Mh] Termos MeSH primário: Analgésicos não Entorpecentes/uso terapêutico
Dor Crônica/tratamento farmacológico
Neuralgia/tratamento farmacológico
ômega-Conotoxinas/uso terapêutico
[Mh] Termos MeSH secundário: Analgésicos não Entorpecentes/efeitos adversos
Bloqueadores dos Canais de Cálcio/efeitos adversos
Bloqueadores dos Canais de Cálcio/uso terapêutico
Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
ômega-Conotoxinas/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics, Non-Narcotic); 0 (Calcium Channel Blockers); 0 (omega-Conotoxins); 7I64C51O16 (ziconotide)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160211
[St] Status:MEDLINE


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[PMID]:26861471
[Au] Autor:Pope JE; Deer TR; Amirdelfan K; McRoberts WP; Azeem N
[Ad] Endereço:Center for Pain Relief, Charleston, WV, USA. United States.
[Ti] Título:The Pharmacology of Spinal Opioids and Ziconotide for the Treatment of Non-Cancer Pain.
[So] Source:Curr Neuropharmacol;15(2):206-216, 2017.
[Is] ISSN:1875-6190
[Cp] País de publicação:United Arab Emirates
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Intrathecal drug delivery has undergone a revitalization following a better understanding of this delivery route and its pharmacokinetics. Driven by patient safety and outcomes, clinicians are motivated to rethink the traditional spinal infusion pump patient selection criteria and indications. We review the current understanding of the pharmacology of commonly employed intrathecal agents and the clinical relevance. METHODS: Search strategies for data acquisition included Medline database, PubMed, Google scholar, along with international and national professional meeting content, with key words including pharmacology of opioids, intrathecal therapy, ziconotide, pharmacokinetics, and intrathecal drug delivery. The search results were limited to the English language. RESULTS: Over 300 papers were identified. The literature was condensed and digested to evaluate the most commonly used medications in practice, sto serve as a foundation for review. We review on-label medications: ziconotide and morphine, and off label medications including fentanyl, sufentail, and hydromorphine. CONCLUSION: Intrathecal therapy has level-one evidence for use for malignant pain and nonmalignant pain, with continued cost savings and improved safety. To most effectively serve our patients, a clear appreciation for the pharmacology of these commonly employed medication is paramount.
[Mh] Termos MeSH primário: Analgésicos não Entorpecentes/uso terapêutico
Analgésicos Opioides/metabolismo
Dor/tratamento farmacológico
Medula Espinal/metabolismo
ômega-Conotoxinas/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Bases de Dados Bibliográficas/estatística & dados numéricos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics, Non-Narcotic); 0 (Analgesics, Opioid); 0 (omega-Conotoxins); 7I64C51O16 (ziconotide)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160211
[St] Status:MEDLINE


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[PMID]:27454282
[Au] Autor:Staquet H; Dupoiron D; Nader E; Menei P
[Ad] Endereço:Hopital Beaujon, Neurochirurgie, Clichy la Garenne, France, CHU d'Angers, Angers, France.
[Ti] Título:Intracerebroventricular Pain Treatment with Analgesic Mixtures including Ziconotide for Intractable Pain.
[So] Source:Pain Physician;19(6):E905-15, 2016 Jul.
[Is] ISSN:2150-1149
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Intracerebroventricular (ICV) administration of opioids for control of intractable cancer pain has been used since 1982. We present here our experience of intracerebroventricular administration of pain treatments including ziconotide associated with morphine and ropivacaine for patients resistant to a conventional approach, with nociceptive, neuropathic, or mixed pain. These clinical cases were conducted with patients suffering from refractory pain, more than 6/10 on a numerical pain rating scale (NPRS) while on high-dose medical treatment and/or intolerance with significant side effects from oral medication. The baseline study visit included a physical examination and an assessment of pain intensity on a NPRS. Under general anesthesia, a neuronavigation device was used to place the catheter on the floor of the third ventricle, supported by an endoscope. Then, drugs were injected in the cerebroventricular system, through a pump (external or subcutaneous). The primary objective was to measure pain evaluation with ICV treatment after a complete withdrawal of other medications.Four patients were enrolled: 3 with intractable cancer pain and one with central neuropathic pain. The median NPRS at baseline was 9.5 [8.5; 19]. The mean NPRS after one month was 3.5 [3; 4.5]. Ziconotide was initiated at 0.48 µg/d and up to a median of 1.2 µg/d [1.0; 1.56]. The median dose of morphine and ropivacaine used initially was respectively 0.36 mg/d [0.24; 0.66] up to 0.6 mg/d [0.45; 4.63] and 1.2 mg/d [0; 2.4] up to 2.23 mg/d [1.2; 3.35]. Minor side effects were initially observed but transiently. One psychiatric agitation required discontinuation of ziconotide infusion. For intractable pain, using ziconotide by intracerebroventricular infusion seems safe and efficient, specifically for chronic neoplastic pain of cervicocephalic, thoracic, or diffuse origin and also for pain arising from a central neuropathic mechanism.
[Mh] Termos MeSH primário: Dor Intratável/tratamento farmacológico
ômega-Conotoxinas/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Analgésicos/uso terapêutico
Analgésicos Opioides/uso terapêutico
Seres Humanos
Masculino
Meia-Idade
Morfina/uso terapêutico
Manejo da Dor
Dor Intratável/etiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics); 0 (Analgesics, Opioid); 0 (omega-Conotoxins); 76I7G6D29C (Morphine); 7I64C51O16 (ziconotide)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160726
[St] Status:MEDLINE


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[PMID]:26856969
[Au] Autor:McDowell GC; Pope JE
[Ad] Endereço:Integrated Pain Solutions, Columbus, OH, USA.
[Ti] Título:Intrathecal Ziconotide: Dosing and Administration Strategies in Patients With Refractory Chronic Pain.
[So] Source:Neuromodulation;19(5):522-32, 2016 Jul.
[Is] ISSN:1525-1403
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Ziconotide is a non-opioid analgesic for intrathecal (IT) administration. The aim of this review is to provide a comprehensive and clinically relevant summary of the literature on dosing and administration with IT ziconotide in the management of refractory chronic pain, and to describe novel dosing strategies intended to improve clinical outcomes. MATERIALS AND METHODS: A Medline search was conducted for "ziconotide," supplemented by manual searching of published bibliographies and abstracts from conferences. RESULTS: Early experience with IT ziconotide in clinical trials combined with improved understanding of drug pharmacokinetics in the cerebrospinal fluid have led to a reappraisal of approaches to trialing and initiation of continuous-infusion therapy in an effort to improve tolerability. The traditional paradigm of trialing by inpatient continuous infusion may be shifting toward outpatient trialing by IT bolus, although definitions of success and specific protocols remain to be agreed upon. Expert consensus on IT continuous infusion with ziconotide suggests a starting dose of 0.5 to 1.2 mcg/day followed by dose titration of ≤0.5 mcg/day on a no more than weekly basis, according to individual patients' pain reductions and regimen tolerability. DISCUSSION: Newer modalities that include patient-controlled analgesia and nocturnal flex dosing have been shown to hold promise of further improvements in ziconotide efficacy and tolerability. CONCLUSIONS: Clinical trials and experience confirm the feasibility and usefulness of IT ziconotide in the management of refractory chronic pain. Emerging evidence suggests that additional IT delivery options may further expand the usefulness and benefits of ziconotide.
[Mh] Termos MeSH primário: Analgésicos não Entorpecentes/administração & dosagem
Dor Crônica/tratamento farmacológico
Infusão Espinal/métodos
Dor Intratável/tratamento farmacológico
ômega-Conotoxinas/administração & dosagem
[Mh] Termos MeSH secundário: Bases de Dados Bibliográficas/estatística & dados numéricos
Relação Dose-Resposta a Droga
Seres Humanos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics, Non-Narcotic); 0 (omega-Conotoxins); 7I64C51O16 (ziconotide)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160210
[St] Status:MEDLINE
[do] DOI:10.1111/ner.12392


  9 / 803 MEDLINE  
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[PMID]:26732557
[Au] Autor:Manda P; Kushwaha AS; Kundu S; Shivakumar HN; Jo SB; Murthy SN
[Ad] Endereço:Department of Pharmaceutics and Drug Delivery, The University of Mississippi, University, MS 38677, USA.
[Ti] Título:Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain.
[So] Source:J Control Release;224:69-76, 2016 Feb 28.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague-Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v.) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01±0.34h(-1). The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78±6.8ng/mL and ~2h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15min) compared to i.v. administration (120min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54±0.08h(-1) and 0.42±0.10h(-1) respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain.
[Mh] Termos MeSH primário: Analgésicos/líquido cefalorraquidiano
Analgésicos/uso terapêutico
Dor Crônica/tratamento farmacológico
ômega-Conotoxinas/líquido cefalorraquidiano
ômega-Conotoxinas/uso terapêutico
[Mh] Termos MeSH secundário: Administração Intranasal
Administração Intravenosa
Analgésicos/administração & dosagem
Animais
Disponibilidade Biológica
Sistemas de Liberação de Medicamentos
Géis
Injeções Espinhais
Masculino
Mucosa Olfatória/metabolismo
Soluções Farmacêuticas
Ratos
Ratos Sprague-Dawley
Viscosidade
ômega-Conotoxinas/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Analgesics); 0 (Gels); 0 (Pharmaceutical Solutions); 0 (omega-Conotoxins); 7I64C51O16 (ziconotide)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160107
[St] Status:MEDLINE


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[PMID]:26662374
[Au] Autor:Eisapoor SS; Jamili S; Shahbazzadeh D; Ghavam Mostafavi P; Pooshang Bagheri K
[Ad] Endereço:Department of Marine Biology, Faculty of Marine Sciences and Technologies, Science and Research Branch, Islamic Azad University, Tehran, Iran.
[Ti] Título:A New, High Yield, Rapid, and Cost-Effective Protocol to Deprotection of Cysteine-Rich Conopeptide, Omega-Conotoxin MVIIA.
[So] Source:Chem Biol Drug Des;87(5):687-93, 2016 May.
[Is] ISSN:1747-0285
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Almost all conopeptides purified from Conus venoms are cysteine-rich peptides. Among them, omega-conotoxin MVIIA, FDA approved peptide drug (Prialt(®)), selected as a cysteine-rich model that its protection from oxidation is critical during solid phase synthesis. Deprotection of cysteines is a crucial step after peptide synthesis. The current study aimed to set up a new highly efficient deprotection protocol for omega-conotoxin MVIIA. Deprotection was performed based on mercury acetate with significant major modification. The protocol accomplished based on the best molar ratio of peptide/mercury/2-ME that adjusted to 0.2 mm/3 mm/10 mm (50 µg/1 mg/10 µL). The yield and purity of omega-conotoxin MVIIA obtained at 93 and 95%, respectively. The total time of protocol shortened to 90 min instead of 6-20 h in routine methods. In this study, omega-conotoxin MVIIA was recovered in high yield and in the shortest time. Despite of other known protocols, molar ratio adjusted to minimum amount. In conclusion, this protocol would be suggested to cost-effective deprotection of thiol groups for similar cysteine-rich peptides.
[Mh] Termos MeSH primário: Análise Custo-Benefício
Cisteína/análise
ômega-Conotoxinas/química
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão
Eletroforese em Gel de Poliacrilamida
Espectrometria de Massas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (omega-Conotoxins); 7I64C51O16 (ziconotide); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170110
[Lr] Data última revisão:
170110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151215
[St] Status:MEDLINE
[do] DOI:10.1111/cbdd.12702



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