Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP) on ganglionic transmission.

1. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP) caused blockade of ganglionic transmission as evidenced by a marked decrease of the amplitude of evoked post-ganglionic compound action potential of the isolated superior cervical ganglion of rat. 2. This effect was not related to its dopaminergic neurotoxicity since pretreatment with pargyline did not prevent the ganglion-blocking action of MPTP. The effects of MPTP on ganglionic transmission were qualitatively similar to those of its narcotic analgesic analogue meperidine. The effects of both drugs were antagonized by the narcotic antagonist naloxone, indicating that the ganglion-blocking effect of MPTP also involved opiate receptors. 3. Like meperidine and morphine, the ganglion-blocking action of MPTP was reduced when the concentration of Ca2+ in the Locke solution was elevated. The blocking effect of methadone on transmission was not reduced by naloxone or elevated Ca2+. 4. The effect of MPTP on nerve action potential was minimal, indicating that the drug blocked synaptic transmission in the ganglion. 5. These results suggest that MPTP inhibits synaptic transmission in the isolated superior cervical ganglion of the rat, probably by interfering with Ca2+ function.