Patent Evaluation: The Use of Spider Toxins for the Treatment of Neurodegenerative Disease

Summary

Novelty: A series of 3-hydroxyindole-polyamines are claimed as calcium channel antagonists. The isolation of naturally occurring polyamines from spider venom is described along with their use for the treatment of stroke, brain trauma, Alzheimer's disease, seizures and hypertension.

Biology: A number of graphs are given, showing the specified polyamine is capable of reversibly blocking electrical current through calcium channels of GH₄C₁ clonal pituitary cells, and can block up to 45% of the high threshold current remaining during nimodipine treatment of NIE-115 cells. A graph is also given showing a concentration dependence of the block of calcium currents by the specified compound.

Chemistry: A scheme is presented showing how the synthetic polyamines were prepared and the use of this method to synthesize a sample of the natural polyamine and experimental details were given for both the isolation of the spider venom and the synthesis of the polyamine, 3-(aminopropyl-aminopropylaminopropylaminopentylaminocarbonylmethyl)-4-hydroxyindole (DOC1). This indole polyamine is one of nine specificallyl claimed compounds.

Structure: