Spider toxins affecting glutamate receptors: Polyamines in therapeutic neurochemistry

Contrasting Actions of Philanthotoxin-343 and Philanthotoxin-(12) on Human Muscle Nicotinic Acetylcholine Receptors

“…Indeed, a reduction in the number of positive charges reduces antagonism potency by about 10-fold per charge at some receptors (Bruce et al, 1990;Mellor et al, 2003). However, there is substantial evidence that these compounds interact with closed (with potentiation and antagonism) as well as open channel conformations of some classes of excitatory receptor (Jackson and Usherwood, 1988;Usherwood and Blagbrough, 1991;Blagbrough and Usherwood, 1992;Jayaraman et al, 1999;Brier et al, 2002). We have recently shown that removal of either one or both of the secondary amines of PhTX-343, with the consequent reduction in positive charge, enhances rather than reduces antagonist potency at human muscle nAChR (Strømgaard et al, 1999(Strømgaard et al, , 2000(Strømgaard et al, , 2002Brier et al, 2002;Mellor et al, 2003); the most potent compound is the dideaza analog [the structures of are shown in Figs.…”

“…4,3,and 3 indicate the number of methylene groups between the amide/amine groups) (Eldefrawi et al, 1988;Piek and Hue, 1989) is a natural product example of a class of polyamine-containing compounds discovered in certain wasp and spider venoms that noncompetitively antagonize nAChR. In general, natural and synthetic philanthotoxins exhibit properties that are qualitatively similar to those of polyamines, such as spermine and spermidine, but at lower concentrations (Usherwood and Blagbrough, 1991).…”

Neurotoxinas: Perspectivas para a descoberta de novos analgésicos

“…A ação paralisante do veneno é essencial para sobrevivência da aranha. Ela paralisa suas presas, mantendo-as vivas até serem embalsamadas e, posteriormente, utilizadas na sua alimentação (USHERWOOD; BLAGBROUGH, 1991 CAIRRÃO et al, 2002).…”

Efeitos biológicos da peçonha da aranha Parawixia bistriata em ratos: isolamento e caracterização química parcial de uma neurotoxina pró-convulsivante

“…As chamadas poliaminas amidas ou acilpoliaminas (Kawai et al, 1982; Fig. 1A), presentes nas peçonhas de diversas aranhas como a Joro (JSTX, isolada da aranha Nephila clavata, encontrada no Japão), Argiope lobata e até mesmo da vespa solitária Philanthus triangulum, são antagonistas glutamatérgicos não-competitivos (bloqueiam os poros dos canais iônicos) dos receptores tipo RNMDA, RAMPA e também do RCAINATO (Usherwood & Blagbrough, 1991;Brackley et al, 1993;Washburn & Dingledine, 1996;Moe et al, 1998).…”

“…A: Acilpoliaminas descritas em peçonhas de aranhas e vespas solitárias. (Usherwood & Blagbrough, 1991). O retângulo denominado espaçador significa um local da molécula ocupado por diferentes radicais, conforme a espécie.…”