The noradrenergic neurotoxins DSP4 and xylamine bind to opiate receptors.

DSP4 and xylamine compete with [3H]-naloxone for opiate binding sites with IC50 values of approximately 1 microM. This effect can be blocked by excess naloxone but not by the noradrenaline uptake inhibitors cocaine or desipramine. Other drugs containing the 2-chloroalkylamine structure--phenoxybenzamine, dibenamine, chloroethyl clonidine, the cholinotoxin AF-64 and 2-dimethylaminoethyl chloride--were similarly tested. Phenoxybenzamine and dibenamine were also able to compete with [3H]-naloxone for binding at the opiate receptor. Experiments in vivo demonstrated that DSP4, like other opiates, can rapidly reduce LH secretion in the rat. This effect is prevented by naloxone but not by desipramine. These data suggest the use of caution in interpreting the results of experiments in which DSP4 and xylamine are used as "specific" noradrenergic uptake inhibitors or as neurotoxins.