Relative potency of synthetic analogs of Ptychodiscus brevis toxin in depressing synaptic transmission evoked in neonatal rat spinal cord in vitro

Abstract

Effects of Ptychodiscus brevis toxin (PbTx) analogs on the spinal synaptic transmission in neonatal rats in vitro were evaluated. PbTx 1/PbTx 2 had aromatic groups and PbTx 3/PbTx 4 had aliphatic groups. All the analogs depressed monosynaptic reflex (MSR) and polysynaptic reflex (PSR) in a concentration-dependent manner. The maximal depression of MSR (75% from initial) and PSR (96%) was at 84 μM for PbTx 1. Concentration to produce 25% inhibition from initial (IC25) by PbTx 1 for MSR and PSR was ⩽2.8 μM. The maximal depression of MSR (80%) was at 96 μM and PSR (100%) was at 32 μM by PbTx 2. IC25 for MSR and PSR were 5.5 μM and <3.2 μM, respectively. PbTx 3 decreased MSR by 25% maximally (=IC25) at 36 μM. The depression of PSR fluctuated and was maximal (75%) at 108 μM and IC25 was 6.2 μM. PbTx 4 depressed MSR and PSR at the maximum of 35% at 32 μM and IC25 for MSR was 8.3 μM and for PSR was 35 μM. Rank order of potency of toxins for depressing MSR was PbTx 1>PbTx 2≫PbTx 4>PbTx 3; and for PSR it was PbTx 2>PbTx 1>PbTx 3≫PbTx 4. Results indicate that the toxins having aromatic groups exhibited greater neurotoxicity.