Conotoxin- 1st May'09 to 31st May'09

Researchers from Newraxon Inc, have invented an indole compond that can be used for Pain therapy. They have filed a patent for their invention that additionally claims that the invented indole compound can be combined with omega-conotoxin(Ziconotide)-sensitive N- type calcium channel antagonists.

The patent is a PCT application filed on 17th Nov'08 and is just been published on 22nd May'09.

Patent Number: WO2009062319 A1

Patent Title: INDOLE COMPOUNDS AND METHODS FOR TREATING VISCERAL PAIN

Assignee: NEURAXON, INC

Inventors:
MADDAFORD, Shawn
RAMNAUTH, Jailall
RAKHIT, Suman
PATMAN, Joanne
RENTON, Paul
ANNEDI, Subhash, C.
ANDREWS, John, S.
MLADENOVA, Gabriela

Conotoxin 1st May'09 to 31st May'09

On 1st May'09, The University of Queensland, Australia has filed a patent in India for its alpha-conotoxin peptides

Application No: 8574/DELNP/2008

Title: CYCLISED ALPHA-CONOTOXIN PEPTIDES

Applicant: University of Queensland

Corresponding PCT: WO2007118270

Abstract: This invention relates to an oral or enteral pharmaceutical preparation comprising at least one synthetically cyclised alpha-conotoxinpeptide having an amide cyclised backbone such that the peptide has no free N- or C- terminus, said peptide having the ability toinhibit a nicotinic acetylcholine receptor and comprising four cysteine resdues bonded in pairs to form two disulfide bonds, whereinthe N-terminus of the corresponding linear/non-cyclised conotoxin peptide is linked to the C-terminus by a peptide linker, in a vehiclewhich is pharmaceutically suitable for oral or enteral administration.

Conotoxin- 1st April'09 to 30th April'09

alpha-Conotoxin AuIB in Water

Institute for Optoelectronics and Microsystems (ISOM) and ETSII, Universidad Politecnica de Madrid (UPM) presents shape, size, structure, conformational stability, and hydrodynamics of alpha-conotoxin AuIB from very long (0.5 mus) massively parallel molecular dynamics (MD) simulations in full atomistic detail.

The researcher have compared the simulation data with analytical predictions that strongly suggests that diffusivities of rigid biomolecules much larger than the alpha-conotoxin AuIB studied here can be obtained from the coarse-grained shape descriptor (ellipsoid) derived from relatively short MD simulations.

Source: Pubmed
Title: Detailed Atomistic Molecular Dynamics Simulations of alpha-Conotoxin AuIB in Water.
PMID: 19309093

Conotoxin- 1st April'09 to 30th April'09

A research publication in Toxicon from Renmin University of China suggest that "hydroxyproline residue is essential for the structure of conomarphin just like D-Phe13".

Dr. Huang et al, have published the article in the title, "Solution structure of Hyp10Pro variant of conomarphin, a cysteine-free and d-amino-acid containing conopeptide" that explains the unusual post-translational modification of conomarphin implies a unique selectivity of hydroxylation in toxin sequence.

Title: Solution structure of Hyp10Pro variant of conomarphin, a cysteine-free and d-amino-acid containing conopeptide.

Source: Pubmed

PMID: 19375441

Journal: Toxiocon

Conotoxin- 1st April'09 to 30th April'09

Motagally et al from Queens University have published a literature on "Tumor necrosis factor {alpha} activates nuclear factor {kappa}B signalling to reduce N-type voltage-gated Ca2+ current in postganglionic sympathetic neurons" that was published in Journal of Physiology.

The article is based on characterizing the effect of overnight incubation in the inflammatory mediator TNFalpha (1 nM) on VGCC in dissociated neurons from mouse superior mesenteric ganglia (SMG).

Voltage-gated Ca2+ currents (ICa) were measured using the perforated patch clamp technique and the VGCC subtypes present in SMG neurons were estimated based on inhibition by selective VGCC blockers: omega-conotoxin GVIA (300 nM; N-type), nifedipine (10 muM; L-type), and omega-conotoxin MVIIC (300 nM; N, P/Q type).

Article Title: Tumor necrosis factor {alpha} activates nuclear factor {kappa}B signalling to reduce N-type voltage-gated Ca2+ current in postganglionic sympathetic neurons.

Inventor: Motagally MA, Lukewich MK, Chisholm SP, Neshat S, Lomax AE.

Source: Pubmed

PMID: 19403618

Conotoxin- 1st April'09 to 30th April'09

A novel X-conntoxin peptide has been invented that is useful for prophylaxis or for the treatment of pain, inflammation, incontinence, cardiovascular conditions, mood disorders etc.

The novel peptide is invented by Dr. Richard Lewis; Dr. Paul Alewood; Dr. Dianne Alewood and Dr. Elka Palant. Xenome has filed an application for patenting the invention in Oct'08 and is been published in April'09.

The patent No: US20090088389 A1
Patent Title: NOVEL X-CONOTOXIN PEPTIDES (-II)

Conotoxin- 1st April'09 to 30th April'09

Xenome is one of the leading companies in conotoxin research. The company has filed a patent application in the US in June'07, that has been recently published April'09. The inventor Dr. Richard J.Lewis is a well-known Proffesor, IMB- University of Queensland, researcher in the field of Molecular Pharmacology in particular conotoxin and pain pathways.

The invention disclose a synergistic combination of a selective inhibitor of the neuronal norepinephrine transporter and an analgesic agent (ω-conotoxin) in the therapeutic management of vertebrate animals, including humans, for the prevention or alleviation of pain, particularly moderate to severe pain.

Patent No: US20090105129 A1

Patent Title: Combination therapy

Source: USPTO

Partial compensation for N-type Ca(2+) channel loss by P/Q-type Ca(2+) channels underlines the differential release properties supported by these chan

Authors: Ladera C, Martín R, Bartolomé-Martín D, Torres M, Sánchez-Prieto J.

Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.

N-type and P/Q-type Ca(2+) channels support glutamate release at central synapses. To determine whether the glutamate release mediated by these channels exhibits distinct properties, we have isolated each release component in cerebrocortical nerve terminals from wild-type mice by specifically blocking N-type Ca(2+) channels with omega-conotoxin-GVIA and P/Q-type Ca(2+) channels with omega-agatoxin-IVA. In addition, we have determined the release properties at terminals from mice lacking the alpha(1B) subunit of N-type channels (Ca(v) 2.2) to test the possibility that P/Q-type channels can compensate for the loss of N-type Ca(2+) channels. We recently demonstrated that, while evoked glutamate release depends on P/Q- and N-type channels in wild-type nerve terminals, only P/Q-type channels participate in these knockout mice. Moreover, in nerve terminals expressing solely P/Q-type channels, metabotropic glutamate receptor 7 (mGluR7) fails to inhibit the evoked Ca(2+) influx and glutamate release. Here, we show that the failure of mGluR7 to modulate evoked glutamate release is not due to a lack of receptors, as nerve terminals from mice lacking N-type Ca(2+) channels express mGluR7. Indeed, we show that other receptor responses, such as the inhibition of forskolin-induced release, are preserved in these knockout mice. N-type channels are more loosely coupled to release than P/Q-type channels in nerve terminals from wild-type mice, as reflected by the tighter coupling of release in knockout nerve terminals. We conclude that the glutamate release supported by N- and P/Q-type channels exhibits distinct properties, and that P/Q-type channels cannot fully compensate for the loss of N-type channels.

Source: Pubmed

Detailed Atomistic Molecular Dynamics Simulations of alpha-Conotoxin AuIB in Water

Authors: Karayiannis NC, Laso M, Kröger M.

Institute for Optoelectronics and Microsystems (ISOM) and ETSII, Universidad Politecnica de Madrid (UPM), Jose Gutierrez Abascal 2, E-28006 Madrid, Spain.

We present results about the shape, size, structure, conformational stability, and hydrodynamics of alpha-conotoxin AuIB (a disulfide-rich peptide from the venom of Conus aulicus, recognized as a nicotinic acetylcholine antagonist with great pharmaceutical potential) from very long (0.5 mus) massively parallel molecular dynamics (MD) simulations in full atomistic detail. We extract coarse-grained descriptors of protein shape (ellipsoid), and of translational and rotational mobilities, i.e., the basic components at the lowest hierarchical level in a multiscale modeling strategy. Structural analysis reveals the folded conformation and asymmetric shape to be strongly favored for conotoxin. In accordance with experimental findings, conformational stability is observed and found to be linked to the presence of the alpha-helix along the 15 residues and to the existence of the two disulfide bonds. We find rotational (D(r)) and translational (D(t)) diffusivities to be suitable descriptors of coarse-grained dynamics, i.e., of the hydrodynamic behavior, and obtain D(r) = 3.62 (+/-0.17) x 10(8) s(- 1) and D(t) = 1.08 (+/-0.4) x 10(- 10) m(2) s(- 1). We further compare the MD-computed coarse-grained descriptors with first principles theoretical predictions based on the extended Hess-Doi Fokker-Planck approach which relates particle shape and dimensions to diffusion coefficients. An excellent agreement between simulation data and analytical predictions is observed for both dynamical descriptors. This comparison strongly suggests that diffusivities of rigid biomolecules much larger than the alpha-conotoxin AuIB studied here can be obtained from the coarse-grained shape descriptor (ellipsoid) derived from relatively short MD simulations.

Inhibition of transmitter release from rat sympathetic neurons via presynaptic M(1) muscarinic acetylcholine receptors.

Authors: Kubista H, Kosenburger K, Mahlknecht P, Drobny H, Boehm S.

Centre of Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.

Background and purpose: M(2), M(3) and/or M(4) muscarinic acetylcholine receptors have been reported to mediate presynaptic inhibition in sympathetic neurons. M(1) receptors mediate an inhibition of K(v)7, Ca(V)1 and Ca(V)2.2 channels. These effects cause increases and decreases in transmitter release, respectively, but presynaptic M(1) receptors are generally considered facilitatory. Here, we searched for inhibitory presynaptic M(1) receptors. Experimental approach: In primary cultures of rat superior cervical ganglion neurons, Ca(2+) currents were recorded via the perforated patch-clamp technique, and the release of [(3)H]-noradrenaline was determined. Key results: The muscarinic agonist oxotremorine M (OxoM) transiently enhanced (3)H outflow and reduced electrically evoked release, once the stimulant effect had faded. The stimulant effect was enhanced by pertussis toxin (PTX) and was abolished by blocking M(1) receptors, by opening K(v)7 channels and by preventing action potential propagation. The inhibitory effect was not altered by preventing action potentials or by opening K(v)7 channels, but was reduced by PTX and omega-conotoxin GVIA. The inhibition remaining after PTX treatment was abolished by blockage of M(1) receptors or inhibition of phospholipase C. When [(3)H]-noradrenaline release was triggered independently of voltage-activated Ca(2+) channels (VACCs), OxoM failed to cause any inhibition. The inhibition of Ca(2+) currents by OxoM was also reduced by omega-conotoxin and PTX and was abolished by M(1) antagonism in PTX-treated neurons. Conclusions and implications: These results demonstrate that M(1), in addition to M(2), M(3) and M(4), receptors mediate presynaptic inhibition in sympathetic neurons using phospholipase C to close VACCs.

Source: Pubmed

Neuroprotective and cardioprotective conopeptides: an emerging class of drug leads.

Authors: Twede VD, Miljanich G, Olivera BM, Bulaj G.

Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA.

The peptides in the venoms of predatory marine snails belonging to the genus Conus ('cone snails') have well-established therapeutic applications for the treatment of pain and epilepsy. This review discusses the neuroprotective and cardioprotective potential of four families of Conus peptides (conopeptides), including omega-conotoxins that target voltage-gated Ca2+ channels, conantokins that target NMDA receptors, mu-conotoxins that target voltage-gated Na+ channels, and kappa- and kappaM-conotoxins that target K+ channels. The diversity of Conus peptides that have already been shown to exhibit neuroprotective/cardioprotective activity suggests that marine snail venoms are a potentially rich source of drug leads with diverse mechanisms.

Conotoxin- 1st Feb'09 to 28th Feb'09

PMID: 19221121
Interaction between the second messengers cAMP and Ca2+ in mouse Presynaptic taste cells.
Roberts CD, Dvoryanchikov G, Roper SD, Chaudhari N.

PMID: 19217942
Soluble expression and one-step purification of a neurotoxin Huwentoxin-I in Escherichia coli.
Che N, Wang L, Gao Y, An C.

PMID: 19210780
Binding of long-chain alpha-neurotoxin would stabilize the resting state of nAChR: A comparative study with alpha-conotoxin.
Nasiripourdori A, Ranjbar B, Naderi-Manesh H.

PMID: 19206132
Integrated Oxidative Folding of Cysteine/Selenocysteine Containing Peptides: Improving Chemical Synthesis of Conotoxins.
Walewska A, Zhang MM, Skalicky JJ, Yoshikami D, Olivera BM, Bulaj G.

PMID: 19187447
ACTIVATION OF PRESYNAPTIC M-TYPE K(+) CHANNELS INHIBITS [H]D-ASPARTATE RELEASE BY REDUCING Ca(2+) ENTRY THROUGH P/Q-TYPE VOLTAGE-GATED Ca(2+) CHANNELS.
Luisi R, Panza E, Barrese V, Iannotti FA, Viggiano D, Secondo A, Canzoniero LM, Martire M, Annunziato L, Taglialatela M.

PMID: 19187266
alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex.
Livingstone PD, Srinivasan J, Kew JN, Dawson LA, Gotti C, Moretti M, Shoaib M, Wonnacott S.

PMID: 19165896
Structural studies of conotoxins.
Daly NL, Craik DJ.

PMID: 19125616
Structure and activity of (2,8)-dicarba-(3,12)-cystino alpha-ImI, an alpha-conotoxin containing a nonreducible cystine analogue.
MacRaild CA, Illesinghe J, van Lierop BJ, Townsend AL, Chebib M, Livett BG, Robinson AJ, Norton RS.

PMID: 19098004
Inhibition of Neuronal Nicotinic Acetylcholine Receptor Subtypes by {alpha}-Conotoxin GID and Analogues.
Millard EL, Nevin ST, Loughnan ML, Nicke A, Clark RJ, Alewood PF, Lewis RJ, Adams DJ, Craik DJ, Daly NL.

PMID: 19089803
A room temperature ionic liquid as convenient solvent for the oxidative folding of conopeptides.
Miloslavina AA, Leipold E, Kijas M, Stark A, Heinemann SH, Imhof D.

PMID: 19029195
Toluene can perturb the neuronal voltage-dependent Ca2+ channels involved in the middle-ear reflex.
Maguin K, Campo P, Parietti-Winkler C.

PMID: 19010337
Antinociceptive effects of the marine snail peptides conantokin-G and conotoxin MVIIA alone and in combination in rat models of pain.
Hama A, Sagen J.

PMID: 18845633
N-type Ca(2+) -channels in murine pancreatic beta-cells are inhibited by an exclusive coupling with somatostatin receptor subtype 1.
Smith PA.

PMID: 18824011
N-type and P/Q-type calcium channels regulate differentially the release of noradrenaline, ATP and beta-NAD in blood vessels.
Smyth LM, Yamboliev IA, Mutafova-Yambolieva VN.

Conus Venom - The University of Queensland

Professor Adams, along with Professor David Craik and colleagues from the University of Queensland's Institute for Molecular Bioscience, have described a surprising new way of inhibiting pain sensors using mini-proteins commonly found in cone snail venoms.

“For several years, it's been known that the remarkable properties of cone shell toxins (conotoxins) hold tremendous promise for chronic pain sufferers, and drugs that can combat or alleviate pain are a holy grail in drug discovery,” Professor Adams said.

The research paper of Professor David Adams invites scientists around the world to reconsider the conventional model for how conotoxins act on target cells such as sensory neurons, opening up what could be a paradigm shift in the development of conotoxin-based therapeutics and analgesics.


Source: Physorg

Conotoxin- 1st Oct'08 to 31st Oct'08

PMID: 19013796
Molecular modeling of the alpha9alpha10 nicotinic acetylcholine receptor subtype.
Pérez EG, Cassels BK, Zapata-Torres G.

PMID: 19010337
Antinociceptive effects of the marine snail peptides conantokin-G and conotoxin MVIIA alone and in combination in rat models of pain.
Hama A, Sagen J.

PMID: 18992939
NR2B-selective conantokin peptide inhibitors of the NMDA receptor display enhanced antinociceptive properties compared to non-selective conantokins.
Xiao C, Huang Y, Dong M, Hu J, Hou S, Castellino FJ, Prorok M, Dai Q.

PMID: 18971294
omega-conotoxin GVIA alters gating charge movement of N-type (CaV2.2) calcium channels.
Yarotskyy V, Elmslie KS.

PMID: 18951936
Osthole and imperatorin, the active constituents of Cnidium monnieri (L.) Cusson, facilitate glutamate release from rat hippocampal nerve terminals.
Wang SJ, Lin TY, Lu CW, Huang WJ.

PMID: 18948615
Presynaptic prostaglandin E2 EP1-receptor facilitation of cerebral nitrergic neurogenic vasodilation.
Jadhav V, Jabre A, Chen MF, Lee TJ.

PMID: 18948154
Peptide pal9a from the venom of the turrid snail Polystira albida from the Gulf of Mexico: Purification, characterization, and comparison with P-conotoxin-like (framework IX) conoidean peptides.
Aguilar MB, de la Rosa RA, Falcón A, Olivera BM, Heimer de la Cotera EP.

PMID: 18945902
Analgesic alpha-conotoxins Vc1.1 and Rg1A inhibit N-type calcium channels in rat sensory neurons via GABAB receptor activation.
Callaghan B, Haythornthwaite A, Berecki G, Clark RJ, Craik DJ, Adams DJ.

PMID: 18930043
Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration.
Glick SD, Sell EM, Maisonneuve IM.

PMID: 18922949
Differential Inhibition of Ca2+ channels by alpha2-adrenoceptors in three functional subclasses of rat sympathetic neurons.
Li C, Horn JP.

PMID: 18845633
N-type Ca(2+) -channels in murine pancreatic beta-cells are inhibited by an exclusive coupling with somatostatin receptor subtype 1.
Smith PA.

PMID: 18831583
NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to the mu-conotoxin SxIIIA.
Walewska A, Skalicky JJ, Davis DR, Zhang MM, Lopez-Vera E, Watkins M, Han TS, Yoshikami D, Olivera BM, Bulaj G.

PMID: 18798648
Structure, dynamics, and selectivity of the sodium channel blocker mu-conotoxin SIIIA.
Yao S, Zhang MM, Yoshikami D, Azam L, Olivera BM, Bulaj G, Norton RS.

PMID: 18788721
Conformational simulations of aqueous solvated alpha-conotoxin GI and its single disulfide analogues using a polarizable force field model.
Jiang N, Ma J.

PMID: 18653802
Access and binding of local anesthetics in the closed sodium channel.
Bruhova I, Tikhonov DB, Zhorov BS.

PMID: 18644398
omega-Conotoxin inhibition of excitatory synaptic transmission evoked by dorsal root stimulation in rat superficial dorsal horn.
Motin L, Adams DJ.

PMID: 18588930
alpha4/7-conotoxin Lp1.1 is a novel antagonist of neuronal nicotinic acetylcholine receptors.
Peng C, Han Y, Sanders T, Chew G, Liu J, Hawrot E, Chi C, Wang C.

PMID: 18523965
Identification and characterization of a novel O-superfamily conotoxin from Conus litteratus.
Wang L, Pi C, Liu J, Chen S, Peng C, Sun D, Zhou M, Xiang H, Ren Z, Xu A.

Conotoxin- 1st Dec'08 to 31st Dec'08

PMID: 19118590
Structural characterization of five post-translationally modified isomorphs of a novel putative delta-conotoxin from the vermivorous snail Conus delessertii from the Mexican Caribbean Sea.
Aguilar MB, Flores-Torres A, Batista CV, Falcón A, López-Vera E, de la Cotera EP.

PMID: 19109404
GLUCAGON-LIKE PEPTIDE-2 RELAXES MOUSE STOMACH THROUGH VASOACTIVE INTESTINAL PEPTIDE RELEASE.
Amato A, Baldassano S, Serio R, Mule F.

PMID: 19107760
Structurally Minimized mu-Conotoxin Analogues as Sodium Channel Blockers: Implications for Designing Conopeptide-Based Therapeutics.
Han TS, Zhang MM, Walewska A, Gruszczynski P, Robertson CR, Cheatham Iii TE, Yoshikami D, Olivera BM, Bulaj G.

PMID: 19098004
Inhibition of Neuronal Nicotinic Acetylcholine Receptor Subtypes by {alpha}-Conotoxin GID and Analogues.
Millard EL, Nevin ST, Loughnan ML, Nicke A, Clark RJ, Alewood PF, Lewis RJ, Adams DJ, Craik DJ, Daly NL.

PMID: 19091927
Abolishment of Serotonergic Neurotransmission to Cardiac Vagal Neurons During and After Hypoxia and Hypercapnia with Prenatal Nicotine Exposure.
Kamendi HW, Cheng Q, Dergecheva O, Gorini C, Jameson HS, Wang X, McIntosh JM, Mendelowitz D.

PMID: 19073169
Cyanocobalamin, vitamin B12, depresses glutamate release through inhibition of voltage-dependent Ca2+ influx in rat cerebrocortical nerve terminals (synaptosomes).
Hung KL, Wang CC, Huang CY, Wang SJ.

PMID: 19055493
Seletracetam (ucb 44212) inhibits high-voltage-activated Ca(2+) currents and intracellular Ca(2+) increase in rat cortical neurons in vitro.
Martella G, Bonsi P, Sciamanna G, Platania P, Madeo G, Tassone A, Cuomo D, Pisani A.

PMID: 19034250
Intrathecal therapy with ziconotide: clinical experience and considerations on its use.
Vitale V, Battelli D, Gasperoni E, Monachese N.

PMID: 18951936
Osthole and imperatorin, the active constituents of Cnidium monnieri (L.) Cusson, facilitate glutamate release from rat hippocampal nerve terminals.
Wang SJ, Lin TY, Lu CW, Huang WJ.

PMID: 18930043
Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration.
Glick SD, Sell EM, Maisonneuve IM.

PMID: 18922949
Differential Inhibition of Ca2+ channels by alpha2-adrenoceptors in three functional subclasses of rat sympathetic neurons.
Li C, Horn JP.

PMID: 18831999
Reverse Na(+)/Ca(2+)-exchange mediated Ca(2+)-entry and noradrenaline release in Na(+)-loaded peripheral sympathetic nerves.
Török TL, Rácz D, Sáska Z, Dávid AZ, Tábi T, Zillikens S, Nada SA, Klebovich I, Gyires K, Magyar K.

PMID: 18792989
Mechanisms underlying the honokiol inhibition of evoked glutamate release from glutamatergic nerve terminals of the rat cerebral cortex.
Sy HN, Wu SL, Wang WF, Wang SJ.

PMID: 18783734
Hidden diversity in a hyperdiverse gastropod genus: discovery of previously unidentified members of a Conus species complex.
Duda TF Jr, Bolin MB, Meyer CP, Kohn AJ.

PMID: 18683240
Excitatory effects of low-level lead exposure on action potential firing of pyramidal neurons in CA1 region of rat hippocampal slices.
Yan D, Xiao C, Ma FL, Wang L, Luo YY, Liu J, Wang HL, Chen JT, Ruan DY.

Conotoxin-1st Nov'08 to 30th Nov'08

PMID: 19075488
Vasodilatory effect of cilnidipine, an L-type and N-type calcium channel blocker, on rat kidney glomerular arterioles.
Konno Y, Kimura K.

PMID: 19029195
Toluene can perturb the neuronal voltage-dependent Ca2+ channels involved in the middle-ear reflex.
Maguin K, Campo P, Parietti-Winkler C.

PMID: 19028470
Prenatal exposure of rats to nicotine causes persistent alterations of nicotinic cholinergic receptors.
Gold AB, Keller AB, Perry DC.

PMID: 19004821
Deletion of N-type Ca2+ Channel Cav2.2 Results in Hyperaggressive Behaviors in Mice.
Kim C, Jeon D, Kim YH, Lee CJ, Kim H, Shin HS.

PMID: 18987848
Effects of subunit selective nACh receptors on operant ethanol self-administration and relapse-like ethanol-drinking behavior.
Kuzmin A, Jerlhag E, Liljequist S, Engel J.

PMID: 18954522
HDT-1, a new synthetic compound, inhibits glutamate release in rat cerebral cortex nerve terminals (synaptosomes).
Wang SJ, Chou SH, Kuo YC, Chou SS, Tzeng WF, Leu JY, Huang RF, Liew YF.

PMID: 18950653
Pruning nature: Biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus.
Holford M, Zhang MM, Gowd KH, Azam L, Green BR, Watkins M, Ownby JP, Yoshikami D, Bulaj G, Olivera BM.

PMID: 18817758
Cholinergic signal transduction in the mouse sphenopalatine ganglion.
Rafalzik S, Pehl U, Ott D, Strotmann J, Wolff M, Gerstberger R.

PMID: 18791189
Effects of clonidine on lidocaine-induced inhibition of axonal transport in cultured mouse dorsal root ganglion neurones.
Hiruma H, Shimizu K, Takenami T, Sugie H, Kawakami T.

PMID: 18775475
Characterization of catecholamine release from deer adrenal medullary chromaffin cells.
Douglas SA, Stevenson KE, Knowles PJ, Bunn SJ.

PMID: 18774645
Analgesic effect in rodents of native and recombinant Ph alpha 1beta toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom.
Souza AH, Ferreira J, Cordeiro Mdo N, Vieira LB, De Castro CJ, Trevisan G, Reis H, Souza IA, Richardson M, Prado MA, Prado VF, Gomez MV.

PMID: 18772200
Calcium-permeable presynaptic AMPA receptors in cerebellar molecular layer interneurones.
Rossi B, Maton G, Collin T.

PMID: 18752844
Mechanisms of unmodified CdSe quantum dot-induced elevation of cytoplasmic calcium levels in primary cultures of rat hippocampal neurons.
Tang M, Wang M, Xing T, Zeng J, Wang H, Ruan DY.

PMID: 18664588
Alpha-conotoxin Arenatus IB[V11L,V16D] [corrected] is a potent and selective antagonist at rat and human native alpha7 nicotinic acetylcholine receptors.
Innocent N, Livingstone PD, Hone A, Kimura A, Young T, Whiteaker P, McIntosh JM, Wonnacott S.

PMID: 18658223
Trans-channel interactions in batrachotoxin-modified rat skeletal muscle sodium channels: kinetic analysis of mutual inhibition between mu-conotoxin GIIIA derivatives and amine blockers.
Ma Q, Pavlov E, Britvina T, Zamponi GW, French RJ.

PMID: 18658222
Trans-channel interactions in batrachotoxin-modified skeletal muscle sodium channels: voltage-dependent block by cytoplasmic amines, and the influence of mu-conotoxin GIIIA derivatives and permeant ions.
Pavlov E, Britvina T, McArthur JR, Ma Q, Sierralta I, Zamponi GW, French RJ.

PMID: 18627035
Topology and patch-clamp analysis of the sodium channel in relationship to the anti-lipid a antibody in campylobacteriosis.
Usuki S, Nakatani Y, Taguchi K, Fujita T, Tanabe S, Ustunomiya I, Gu Y, Cawthraw SA, Newell DG, Pajaniappan M, Thompson SA, Ariga T, Yu RK.

Source: Pubmed

Conotoxin-1st Jan'09 to 31st Jan'09

PMID: 19187266
Alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex.
Livingstone PD, Srinivasan J, Kew JN, Dawson LA, Gotti C, Moretti M, Shoaib M, Wonnacott S.

PMID: 19184584
Conotoxins: molecular and therapeutic targets.
Lewis RJ.

PMID: 19171133
Molecular mechanism of KCl-induced relaxation of the esophagus.
Yaktubay Döndaş N, Karataş Y, Kaya D, Soylu N, Singirik E, Baysal F.

PMID: 19170536
Structure of the Analgesic mu-Conotoxin KIIIA and Effects on the Structure and Function of Disulfide Deletion (dagger) (double dagger).
Khoo KK, Feng ZP, Smith BJ, Zhang MM, Yoshikami D, Olivera BM, Bulaj G, Norton RS.

PMID: 19166832
Histological protection by cilnidipine, a dual L/N-type Ca(2+) channel blocker, against neurotoxicity induced by ischemia-reperfusion in rat retina.
Sakamoto K, Kawakami T, Shimada M, Yamaguchi A, Kuwagata M, Saito M, Nakahara T, Ishii K.


PMID: 19162562
omega-conotoxin GVIA sensitive calcium channels on preganglionic nerve terminals in mouse pelvic and celiac ganglia.
Jobling P.

PMID: 19131337
The rational design of alpha -conotoxin analogues targeting alpha 7 nicotinic acetylcholine receptors: Improved antagonistic activity by incorporation of proline derivatives.
Armishaw C, Jensen AA, Balle T, Clark RJ, Harpsøe K, Skonberg C, Liljefors T, Strømgaard K.

PMID: 19094061
Diacylglycerol analogues activate second messenger-operated calcium channels exhibiting TRPC-like properties in cortical neurons.
Tu P, Kunert-Keil C, Lucke S, Brinkmeier H, Bouron A.

PMID: 19073169
Cyanocobalamin, vitamin B12, depresses glutamate release through inhibition of voltage-dependent Ca2+ influx in rat cerebrocortical nerve terminals (synaptosomes).
Hung KL, Wang CC, Huang CY, Wang SJ.

PMID: 19028470
Prenatal exposure of rats to nicotine causes persistent alterations of nicotinic cholinergic receptors.
Gold AB, Keller AB, Perry DC.

PMID: 19013796
Molecular modeling of the alpha9alpha10 nicotinic acetylcholine receptor subtype.
Pérez EG, Cassels BK, Zapata-Torres G.

PMID: 19004821
Deletion of N-type Ca2+ Channel Cav2.2 Results in Hyperaggressive Behaviors in Mice.
Kim C, Jeon D, Kim YH, Lee CJ, Kim H, Shin HS.

PMID: 19003899
Enhanced microwave-assisted method for on-bead disulfide bond formation: Synthesis of alpha-conotoxin MII.
Galanis AS, Albericio F, Grøtli M.

PMID: 18971294
{omega}-Conotoxin GVIA Alters Gating Charge Movement of N-Type (CaV2.2) Calcium Channels.
Yarotskyy V, Elmslie KS.

PMID: 18950653
Pruning nature: Biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus.
Holford M, Zhang MM, Gowd KH, Azam L, Green BR, Watkins M, Ownby JP, Yoshikami D, Bulaj G, Olivera BM.

PMID: 18948615
Presynaptic prostaglandin E2 EP1-receptor facilitation of cerebral nitrergic neurogenic vasodilation.
Jadhav V, Jabre A, Chen MF, Lee TJ.

Conotoxin

Patents on Conotoxin

Conotoxins: Conotoxins are neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus. Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However it appears that many of these peptides modulate the activity of ion channels.

Patents: There are totally about 560 patent documents that are published across various countires including Australia (AU), Brazil (BR), Germany (DE), Denmark (DK), Europe (EP), France (FR), Great Britain (GB), Israel (IL), India (IN), Japan (JP), Korea (KR), Sweden (SE) and The United States of America (US)

The first patent published on conotoxin is JP60226899A titled, Conotoxin Analog by Ajinomoto Co Inc. A few key assignees with respect to patenting activity are listed below along with the number of patents, each assignee own.



 UNIV UTAH RES FOUND (26)
 BRAINCELLS INC (12)
 SIRTRIS PHARMACEUTICALS INC (12)
 AJINOMOTO KK (10)
 NEUROMED TECH INC (8)
 COGNETIX INC (7)
 DYNOGEN PHARMACEUTICALS INC (7)
 MICROBIA INC (7)
 BRIGHAM & WOMENS HOSPITAL (6)
 NEWRON PHARM SPA (6)
 PAINCEPTOR PHARMA CORP (6)
 UNIV CALIFORNIA (6)
 UNIV QUEENSLAND (6)
 UNIV TEXAS (6)
 UNIV UTAH (6)
 HARVARD COLLEGE (5)
 PFIZER (5)
 UNIV JOHNS HOPKINS (5)
 HIBERNATION THERAPEUTICS LTD (4)
 MASSACHUSETTS INST TECHNOLOGY (4)
 UNIV COLUMBIA (4)
 WYETH CORP (4)
 AFFYMAX TECH NV (3)
 ALLERGAN INC (3)
 AMGEN INC (3)
 CAMBRIDGE NEUROSCIENCE INC (3)
 EISAI CO LTD (3)
 ELAN PHARM INC (3)
 GEN HOSPITAL CORP (3)
 MERCK & CO INC (3)
 METABOLIC PHARM LTD (3)
 NEUREX CORP (3)
 ONO PHARMACEUTICAL CO (3)
 SALK INST BIOTECH IND (3)
 SOLVAY PHARM BV (3)
 UNIV LELAND STANFORD JUNIOR (3)
 UNIV MARYLAND (3)
 UNIV SYDNEY (3)
 WARNER LAMBERT CO (3)
 A & G PHARMACEUTICAL INC (2)
 ABBOTT GMBH (2)
 CHILDRENS MEDICAL CENTER (2)
 CYPROS PHARM CORP (2)
 GLOBAL CARDIAC SOLUTIONS PTY L (2)
 IONIX PHARMACEUTICALS LTD (2)
 LILLY INDUSTRIES LTD (2)
 NAT CT FOR BIOLOG SCIENCES (2)
 NUVELO INC (2)
 PHARMACIA CORP (2)
 POINT THERAPEUTICS INC (2)
 PPL THERAPEUTICS SCOTLAND LTD (2)
 UAB RESEARCH FOUNDATION (2)
 UNIV BROWN RES FOUND (2)
 UNIV OREGON HEALTH & SCIENCE (2)
 UNIV ROCHESTER (2)
 US ARMY (2)
 US HEALTH (2)
 ZENECA LTD (2)

Keep watching the blog for more insights and updates on conotoxin with respect to latest patents and literatures across the world.

You are most welcome to comment and suggest on the post, and get back to me for any detail regarding the post (Patent nos, Current researchers, research institutes etc.).