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Millipedes have long been known to produce structurally diverse chemical defenses, including hydrogen cyanide, terpenoid alkaloids, and oxidized aromatics. Although the hydrogen cyanide and oxidized aromatic producing millipedes have been well studied, less than 10% of the terpenoid alkaloid producers have been chemically investigated. Several previous studies have shown that alkaloids disorient predators, but their biochemical target is currently unknown. Herein, we investigated the defensive secretions of a colobognath millipede, Ischnocybe plicata, and elucidated the constitution, absolute configuration, and conformation of four new highly oxidized terpenoid alkaloids, termed ischnocybines, using a range of analytical techniques. The ischnocybines are actively secreted from the defensive glands and were shown to disorient ants, a likely common predator. Evaluation of the ischnocybines in a panel of neuroreceptors revealed that ischnocybine A possesses potent (Ki13.6 nM) and selective (100-fold) binding affinity for sigma-1, an orphan neuroreceptor, over sigma-2. These molecules represent the most complex alkaloids to be discovered from millipedes and provide the first potential insights into a biochemical target responsible for their defensive properties.