Abstract:
N'-coumaroyl spermidine (NlCSpd) is a plant derived chemical which is proposed to
belong to a class of low molecular weight neuroactive substances called phenolic polyamines.
NlCSpd is stnicturally similar to glutamate receptor blocking toxins found in certain spiders and
wasps, such as JSTX-3 and NSTX-3 found in Nephila spiders.
The goal of the present study was to determine if plant-derived phenolic polyamines act
like other structurally related chemicals found in Arthropod venoms, such as JSTX-3, and
whether they can be classified in the same pharmacological group as the spider and wasp toxins.
A comparison was made to determine the relative potencies of various phenolic polyamines fi-om
plants and insect venoms. This comparison was done by measuring the effect of various
concentrations ofNlCSpd on the amplitude of excitatory postsynaptic potentials (EPSPs) elicited
in muscle of the crayfish Proccanbarus clarkii. NlCSpd was also tested on L-glutamate induced
potentials to determine if a postsynaptic component to sj^naptic block occurs.
NlCSpd and an analogue with an a longer polyamine chain, NlCSpm, blocked EPSPs in a
dose dependent manner, NlCSpd having an IC50 of lOOnM. NlCSpd also blocked L-glutamate
induced potentials. The two main components of the NlCSpd molecule alone are insufficient for
activity.
NlCSpd acts postsynaptically by interfering with crayfish glutamatergic synaptic
transmission, likely blocking glutamate receptors by interacting with the same site(s) as other
phenolic polyamines. Certain moieties on the polyamines molecule are necessary for activity while
others are not.
