Studies on curare-like action of the tripeptide carbobenzoxy-Gly-Gly-Arg-β-naphthylamide in mouse diaphragm

Suramin protects the murine motor nerves from the toxic effects of presynaptic Ca 2+ channel inhibitors

“…The possible mechanism of suramin on the depressant effect of presynaptic Ca 21 toxins is that suramin occupies the presynaptic P-type Ca 21 channels and then prevents the further binding by presynaptic Ca 21 neurotoxins. This contention is in agreement with the previous ®nding that suramin can reverse the neuromuscular blocking actions of the non-depolarizing muscle relaxant such as d-tubocurarine [1,2] and tripeptide carbobezoxy-GLY-GLY-GLY-ARG-naphthylamide [7], but not the depolarizing muscle relaxant succinylcholine. We still don't know why suramin has antagonistic effects both on the postsynaptic nicotinic acetylcholine (ACh) receptor, e.g.…”

“…Since suramin is a polysulfate anionic compound with rich negative charges, thus whether the rich negative charges of suramin to produce an interactive effect with the positive charges of presynaptic neurotoxins still need for further investigation. However, suramin cannot inhibit the neuromuscular blocking effect of a postsynaptic neurotoxin, a-bungarotoxin [7], suggesting that this presynaptic effect seems not absolutely dependent on the rich negative charges of suramin. Both v-agatoxin IVA and v-conotoxin MVIIC, the antagonists of P-type Ca 21 channels, blocked transmitter release from nerve endings [6,12].…”

Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine

“…Suramin is also an antagonist of P2 purinoceptors (Dunn and Blakeley, 1988;Inoue et al, 1991). Previously, we have demonstrated that suramin can reverse the inhibitory action of a tripeptide, carbobenzoxy-Gly-Gly-Arg-β-naphthylamide, which acts both at the postsynaptic nACh receptors and presynaptic autoreceptors (Lin-Shiau and Lin, 1998). Recently, a series of novel suramin analogues have been developed (Kassack et al, 2004;Ullmann et al, 2005) that are specifically designed for antitumor activity (Krejci et al, 2010).…”