Conopeptides: From deadly venoms to novel therapeutics

Shen, Gregory S.; Layer, Richard T.; McCabe, R. Tyler

doi:10.1016/s1359-6446(99)01454-3

Cited by 53 publications

(37 citation statements)

References 52 publications

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“…Intrathecal infusion of a selective N-type voltage-operated calcium channel antagonist, o-conotoxin MVIIA (SNX111 or ziconotide), is under clinical trial for the treatment of opioidresistant neuropathic pain in patients with cancer or AIDS (Brose et al, 1997;Shen et al, 2000). A recent report indicates that some serious side eects are associated with central sites of N-channel blockade and peripheral autonomic dysfunction (Penn & Paice, 2000).…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular and autonomic effects of ω‐conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays

Wright

Robertson

Whorlow

et al. 2000

British J Pharmacology

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1 The eects of a novel N-type voltage-operated calcium channel antagonist, o-conotoxin CVID, were compared with o-conotoxin MVIIA on sympathetic-evoked activation of right atria (RA), small mesenteric arteries (MA) and vasa deferentia (VD) isolated from the rat. Their eects were also compared on blood pressure and cardiovascular re¯exes in conscious rabbits. 2 The pIC 50 values for MVIIA and CVID, respectively, for inhibiting sympathetic-evoked responses were equivalent in RA (8.7 and 8.7) and VD (9.0 and 8.7); however, in MA the values were 8.4 and 7.7. The cardiac to vascular (RA/MA) potency ratios, antilog (plog RA ± plog MA), for MVIIA and CVID were 2 and 10. The oset rates for CVID and MVIIA were rapid, and peptide reapplication caused rapid onset of blockade, suggesting limited desensitization. 3 In the conscious rabbit, CVID and MVIIA (100 mg kg 71 i.v.) caused a similar fall in blood pressure and a tachycardia that rapidly reached maximum. Both peptides decreased the vagal-and sympathetic-mediated components of the barore¯ex, but had no eect on the vagal nasopharyngeal re¯ex. The orthostatic re¯ex to 908 tilt was blocked by MVIIA with sustained postural hypotension for 590 min after administration. In contrast, CVID caused postural hypotension at 30 min which recovered rapidly. 4 Neither CVID nor MVIIA (3 mg kg 71 i.t.) signi®cantly altered cardiovascular variables or autonomic re¯exes. 5 In conclusion, CVID appears to be relatively weak at inhibiting the re¯ex response to tilt consistent with its weaker inhibition of rat mesenteric artery constriction to perivascular nerve stimulation. This may point to subtype N-type calcium channel selectivity.

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Section: Introductionmentioning

confidence: 99%

Cardiovascular and autonomic effects of ω‐conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays

Wright

Robertson

Whorlow

et al. 2000

British J Pharmacology

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“…Pesquisadores, frente às características terapêuticas já observadas, persistem na investigação das conotoxinas à procura de moléculas biologicamente ativas, como peptídeos neuroativos e neuroprotetores, derivados de diferentes espécies venenosas que possam ser aplicados clinicamente (SHEN et al, 2000).…”

Section: Toxinas De Caramujos Marinhosunclassified

“…Eles são predadores de águas tropicais e subtropicais, com aproximadamente 500 espécies, classifi cadas em três grupos, de acordo com o hábito alimentar: vermívoros, moluscívoros e piscívoros (SHEN et al, 2000). As espécies de caramujos marinhos com alvos já estabelecidos incluem C. magus, C. aulicus, C. regius, C. purpurascens, C. imperialis e C. geographus (OLIVERA & TEICHERT, 2007).…”

Section: Toxinas De Caramujos Marinhosunclassified

“…Para sua obtenção, ela é extraída dos ductos de veneno desses animais e purifi cada por fracionamento, pela técnica de cromatografi a líquida de alta efi ciência em fase reversa, baseada em superfície de óxidos inorgânicos (AGUILAR et al, 2009). A toxina purifi cada é composta por pequenos peptídeos, denominados conopeptídeos, variando o tamanho de oito a 31 aminoácidos, enriquecida com pontos de dissulfeto (SHEN et al, 2000), os quais mostraram resultados promissores em estudos experimentais de desordens neurológicas, como epilepsia (MALMBERG et al, 2003), Parkinson, Alzheimer, isquemia medular (LAVOR, 2013) e já são utilizados em síndromes neuropáticas de dores crônicas (LIVETT et al, 2004;MEHDIRATTA & SABERWAL, 2007).…”

Section: Toxinas De Caramujos Marinhosunclassified

“…Sua estabilidade estrutural, facilidade de síntese, elevada especifi cidade de alvo e pequeno tamanho de seus peptídeos, proporcionam-lhes um importante potencial terapêutico (SHEN et al, 2000;LEWIS & GARCIA, 2003;OLIVERA & TEICHERT, 2007). Assim, esta revisão objetiva discorrer sobre a fi siopatologia do TME, com ênfase na importância do cálcio (Ca 2+ ) no mecanismo de morte neuronal, abordando a possível utilização terapêutica das toxinas de caramujo marinho bloqueadoras de canais para Ca 2+ dependentes de voltagem (CCDV).…”

Section: Introductionunclassified

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Perspectivas da aplicação das conotoxinas bloqueadoras de canais para cálcio dependentes de voltagem no trauma medular

et al. 2014

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Receptor Targets in Drug Discovery and Development

Williams

Mehlin

Triggle

2003

Burger's Medicinal Chemistry and Drug Discovery

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Drug discovery has entered a new century with an unheralded wealth of sophisticated technologies and information generation platforms, including the draft map of the human genome, which theoretically will allow the more rapid development of medicines with improved selectivity and safety profiles. To use the bewildering exponential flow of data related to the molecular targets involved in the cause(s) of various diseases and the increasingly sophisticated computer‐based technologies that define the requirements for chemical diversity and diversity space requires an understanding of basic receptor/enzyme theory. The latter, based on the Law of Mass Action, defines the concepts of agonism, antagonism, and more recently, allosteric modulation. The application of receptor/enzyme theory to the practical aspects of lead compound identification and optimization is based on defining structure‐activity relationships (SARs) for a variety of physiological and pharmacological parameters and involves the evaluation of new chemical entities in in vitro and in vivo assays that measure efficacy, selectivity, side effect liability and absorption, distribution, metabolism and excretion, and toxicology. Understanding how knowledge of drug targets has evolved; the challenges to validating new targets, especially those evolving from the genome; and assays beyond high‐throughput screening that provide objective SAR information, as well as designing compounds to interact with these targets that have “druggable” characteristics, are the keys to successful, and by definition, financially viable, drug discovery.

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Conopeptides: From deadly venoms to novel therapeutics

Cited by 53 publications

References 52 publications

Cardiovascular and autonomic effects of ω‐conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays

Cardiovascular and autonomic effects of ω‐conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays

Perspectivas da aplicação das conotoxinas bloqueadoras de canais para cálcio dependentes de voltagem no trauma medular

Receptor Targets in Drug Discovery and Development

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