Abstract：
:Epilepsy is characterised by spontaneous recurrent seizures that are caused by an imbalance between neuronal excitability and inhibition. Since ion channels play fundamental roles in the generation and propagation of action potentials as well as neurotransmitter release at a subset of excitatory and inhibitory synapses, their dysfunction has been linked to a wide variety of epilepsies. Indeed, these unique proteins are the major biological targets for antiepileptic drugs. Selective targeting of a specific ion channel subtype remains challenging for small molecules, due to the high level of homology among members of the same channel family. As a consequence, there is a growing trend to target ion channels with biologics. Venoms are the best known natural source of ion channel modulators, and venom peptides are increasingly recognised as potential therapeutics due to their high selectivity and potency gained through millions of years of evolutionary selection pressure. Here we describe the major ion channel families involved in the pathogenesis of various types of epilepsy, including voltage-gated Na+, K+, Ca2+ channels, Cys-loop receptors, ionotropic glutamate receptors and P2X receptors, and currently available venom-derived peptides that target these channel proteins. Although only a small number of venom peptides have successfully progressed to the clinic, there is reason to be optimistic about their development as antiepileptic drugs, notwithstanding the challenges associated with development of any class of peptide drug.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Chow CY,Absalom N,Biggs K,King GF,Ma Ldoi
10.1016/j.bcp.2020.114043subject
Has Abstractpub_date
2020-11-01 00:00:00pages
114043eissn
0006-2952issn
1873-2968pii
S0006-2952(20)30277-Xjournal_volume
181pub_type
杂志文章,评审abstract：:Oral administration of tobacco to rats for 21 days caused remarkable stimulation of the metabolism of phenacetin, aniline and benzo[a]pyrene, a carcinogen, by hepatic microsomal mixed function oxidases (MFO). Such treatment for 6 days resulted in a small increase in the activities of phenacetin O-dealkylase and aromat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90386-0
更新日期：1982-04-15 00:00:00
abstract：:Approximately 60% of the total particulate phosphodiesterase activity occurring in cardiac tissue was associated with the nuclear fraction. Cyclic GMP phosphodiesterase activity of the purified cardiac nuclear fraction was selectively inhibited by trifluoperazine (I50 = 19 microM) with negligible inhibition (less than...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90447-6
更新日期：1982-03-01 00:00:00
abstract：:Although the induction of cytochromes P450 3A (CYP3A) is relatively well characterized in liver, its inducibility in an easily available tissue such as the peripheral leukocytes is not known. The purpose of this study was, therefore, to determine if CYP3A is inducible in vivo in peripheral leukocytes. Microsomes from ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00095-0
更新日期：1996-06-14 00:00:00
abstract：:The normal sexual dimorphism in murine hepatic hexobarbital metabolism (i.e. females greater than males) was found to be absent in senescent animals. Hexobarbital metabolism, expressed as microsomal activity of hexobarbital hydroxylase and hexobarbital-induced sleep time, in senescent male mice was similar to that in ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90724-1
更新日期：1988-01-15 00:00:00
abstract：:Microsomal epoxide hydrolase (mEH) catalyzes the hydrolysis of epoxide intermediates derived from drugs and environmental chemicals. The response of in vivo (embryo) and in vitro (embryo fibroblast) tests were analyzed using mEH-null and wild-type mice to determine the relative role of maternal and embryonic mEH in th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)00847-x
更新日期：2002-03-15 00:00:00
abstract：:The role of CYP2E1 in ketone-stimulated insulin release was investigated using isolated pancreatic islets of Langerhans and two mammalian insulin secreting pancreatic beta-cell lines engineered to stably express human CYP2E1 (designated BRIN BD11h2E1 and INS-1h2E1). Isolated rat pancreatic islets were shown to express...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2003.10.011
更新日期：2004-03-01 00:00:00
abstract：:Recently, we reported that alterations in topoisomerase II (topo II) activity appear to contribute to mitomycin C (MMC) resistance in HT-29R13 human colon cancer cells under aerobic conditions. In this study, the expression of topo II alpha and topo II beta in parent HT-29 and MMC resistant variant HT-29R13 cells was ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00343-7
更新日期：1996-08-23 00:00:00
abstract：:Metabolism of the synthetic steroid 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-1-propynyl-estra-4,9-dien-3-one (RU486) occurs in the dedifferentiated S-H56-125 variant of Reuber hepatoma. Considering that rat liver cytochrome P450 (P450) monooxygenases are engaged in different oxidative steps of the metab...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90654-f
更新日期：1993-12-03 00:00:00
abstract：:Rats fed 1% paracetamol in the diet failed to grow and a dose-dependent inhibition of growth was observed and found to be independent of hepatoxicity. Addition of 0.5% D- or L-methionine, or L-cysteine to a diet containing 1% paracetamol restored growth. Addition of L-methionine to the drinking water was equally effec...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90048-8
更新日期：1989-01-15 00:00:00
abstract：UNLABELLED:ZD1839 ("Iressa"), a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is currently undergoing preclinical and clinical evaluation in several solid tumors. The present study aimed to assess the effect of ZD1839 in combination with oxaliplatin in the colon cancer cell lines HT-2...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00291-0
更新日期：2003-08-15 00:00:00
abstract：:3-alpha-Methyl substituted digitoxigenin-3-beta-glucoside (methyl-dtg-gluc) displays unusual features, e.g. a high dissociation rate constant from its binding site leading to rapid reversibility of the inotropic and toxic effects, and a flat dose-response curve attaining higher inotropic maxima thus indicating an incr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90059-4
更新日期：1982-08-01 00:00:00
abstract：:Inflammation-induced microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal enzyme that synthesizes prostaglandin E(2) (PGE(2)) downstream of cyclooxygenase-2 (COX-2). The efficacy of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors in the treatment of the signs and symptoms of osteoarthritis, rheuma...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.01.003
更新日期：2010-05-15 00:00:00
abstract：:B-Raf kinase is the key point in a main branch of mitogen-activated protein kinase pathways and some of its mutations, such as the V600E mutation, lead to the persistent activation of ERK signaling and the trigger of severe diseases, including melanoma and other somatic cancers. Several potent drugs have been approved...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.02.022
更新日期：2017-05-15 00:00:00
abstract：:The effect of dichlorvos (200 mg/kg body weight) with or without nimodipine (6 mg/kg body weight/day for 3 days, starting 1 day prior to the administration of dichlorvos) on calcium homeostasis was studied in the rat brain. The delayed neurotoxic potential of dichlorvos was assessed in terms of neuropathy target ester...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00762-6
更新日期：2001-11-01 00:00:00
abstract：:Chronic inflammation has been implicated as the underlying factor in the pathogenesis of many disorders. In the past decade, inflammation-related endogenous production of reactive nitrogen species, similar to oxygen free radicals, has also been suggested as a risk factor for cancer, in addition to the well-studied exo...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00504-2
更新日期：1997-12-15 00:00:00
abstract：:Inflammation, especially chronic inflammation, is directly involvement in the pathogenesis of many diseases including cancer. An effective approach for managing inflammation is to employ chemicals to block activation of nuclear factor-κB (NF-κB), a key regulator for inflammatory processes. Piperlongumine (piplartine, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.03.014
更新日期：2015-06-01 00:00:00
abstract：:Compound 14beta,17beta-cycloketoester-3beta-OH androstane (INCICH-D7) is a semisynthetic product of a structural modification of the digitoxigenin molecule. INCICH-D7 has a heterocyclic ketoester type fusion between positions C14 and C17 of the steroid nucleus, which confers this molecule stronger electronegativity th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.06.020
更新日期：2005-09-15 00:00:00
abstract：:We have studied the effect of low sulfate concentrations on the glycosaminoglycan synthesis in rat patellar cartilage in vivo as well as in vitro. The oral administration of 200 mg/kg paracetamol to male Wistar rats resulted in a significant reduction of the serum sulfate concentration. Reduced serum sulfate availabil...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90401-7
更新日期：1988-10-01 00:00:00
abstract：:Castanospermine (CS) is a potent but non-selective inhibitor of many glycohydrolases including the intestinal disaccharidases. Several CS-glucosides were synthesized to investigate the effect of an attached glucopyranosyl residue on the potency and selectivity of CS toward inhibition of intestinal disaccharidases. 8 a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90518-p
更新日期：1990-05-15 00:00:00
abstract：:Polyphenolic anthocyanins are major colorful compounds in red fruits, known to prevent cardiovascular and other diseases. Grape polyphenols are a mixture of various molecules and their exact contribution to above bioactivities remains to be clarified. In the present study, we first analyzed the effect of purified grap...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.06.010
更新日期：2013-11-15 00:00:00
abstract：:MRS 1754 [N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy]acetamide] is a selective antagonist ligand of A(2B) adenosine receptors. This is the least well-defined adenosine receptor subtype, and A(2B) antagonists have potential as antiasthmatic drugs. For use as a radioligand, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00531-7
更新日期：2001-03-15 00:00:00
abstract：:H-Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH2, a broad spectrum neuropeptide growth factor antagonist (antagonist G), is soon to enter a phase I clinical trial for the treatment of small-cell lung cancer (SCLC). The pre-clinical pharmacology of this peptide has revealed that its metabolism proceeds from the C-terminus via deam...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00191-2
更新日期：1995-08-25 00:00:00
abstract：:Runt-related transcription factor 1 (RUNX1), one subunit of core-binding factors in hematopoiesis and leukemia, was highly expressed in ovarian cancer (OC), but the role of RUNX1 in OC is largely unknown. Since we found that high expression of RUNX1 is correlated with poor survival in patients with OC through bioinfor...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114116
更新日期：2020-10-01 00:00:00
abstract：:Tannic acid (TA) is a naturally occurring phenol, which has been found to display an antipromotion effect on mouse skin carcinogenesis. In order to explore the molecular mechanism, we have examined the process of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced protein kinase C (PKC) activation, including phorbol es...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90095-e
更新日期：1993-10-19 00:00:00
abstract：:2-Chloroacetaldehyde (CAA)-induced cytotoxicity in isolated hepatocytes was enhanced markedly if hepatocyte alcohol or aldehyde dehydrogenase was inhibited prior to CAA addition. Hepatocyte GSH depletion, ATP depletion and lipid peroxidation by CAA were also enhanced markedly. Furthermore, CAA was about 10- and 70-fol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90374-3
更新日期：1994-08-30 00:00:00
abstract：:Multivalent dendrimeric conjugates of GPCR ligands may have increased potency or selectivity in comparison to monomeric ligands, a phenomenon that was tested in a model of cytoprotection in mouse HL-1 cardiomyocytes. Quantitative RT-PCR indicated high expression levels of endogenous A(1) and A(2A) adenosine receptors ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.03.020
更新日期：2010-07-15 00:00:00
abstract：:Membrane damage caused by phospholipase A action is thought to be an important factor in ischemic myocardial injury. Propranolol has been shown previously to have beneficial effects in both animal experiments and clinical trials, and it has membrane-stabilizing properties in vitro. To investigate the possibility that ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90666-6
更新日期：1987-12-15 00:00:00
abstract：:It has become apparent of late that even in tamoxifen and/or aromatase resistant breast cancers, ERα remains a bona fide therapeutic target. Not surprisingly, therefore, there has been considerable interest in developing Selective ER Degraders (SERDs), compounds that target the receptor for degradation. Currently, ICI...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.03.031
更新日期：2011-07-15 00:00:00
abstract：:The effect of 3'-deoxythymidin-2'-ene (d4T) on the metabolism of exogenously supplied radiolabeled nucleosides was investigated. Following a 24-hr exposure to 250 microM d4T, we observed no significant effect on the incorporation of [3H]thymidine or [3H]deoxycytidine into DNA. In contrast, the amounts of [3H]uridine, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90516-n
更新日期：1990-05-15 00:00:00
abstract：:Metabolomics offers the opportunity to uncover endogenous biomarkers that can lead to metabolic pathways and networks and that underpin drug toxicity mechanisms. A novel protocol is presented and discussed that is applicable to drugs which generate urinary metabolites when administered to mice sensitive to its toxicit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2018.09.022
更新日期：2018-10-01 00:00:00
