Neuromuscular Effects of Metal Complexes

The neuromuscular effects of metal chelates may also be attributed to interference, in many cases, of ion transport across membranes. 

The highly charged complex, ruthenium red (Structure 59, Chapter 6) is a powerful and specific inhibitor of calcium transport across mitochondrial membranes [16, 17], similar to the inhibition induced by lanthanides [18]. Significant amounts of the complex may also penetrate into nerve fibers in vivo and in vitro, and induce neurotoxicity [19, 20]. Interestingly, the toxicity is dependent on the route of administration intracranial administration produces convulsions while intraperitioneal injection induces paralysis [21]. 

Calcium ions are critical in the release of neurotransmitter substances at chemical synapses, and intracellular buffering mechanisms, possibly through a Na/K—ATPase mediated exchange [22], are important in controlling the release of Ca ions and thus release of the neurotransmitter. The blocking of calcium transport by ruthenium red increases the spontaneous release of neurotransmitter [23]. The utility of these effects as probes is shown by the fact that acetylcholine release induced by tityustoxin, a scorpion neurotoxin, was shown to be enhanced by ruthenium red the stimulation was Ca-dependent and thus the conclusion was reached that free calcium, caused by competitive binding of ruthenium red to receptors, increased the release of acetylcholine [24]. 

In view of these results, the strong neuromuscular blocking effect of cations such as [Pt(en)3]discovered during the synthesis and testing of platinum complexes, is not really surprising. The unusual difference between the chemically very similar [Pt(en)(oxalato)] (strong neuromuscular inhibition) and [Pt(en)(malonato)] (good antitumour activity, no neuromuscular toxicity at active doses) is however unexplained. A further complex with marked neuromuscular effects is the metallointercalator 

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