Central hypothermic effects of some analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+)

Effects of some MPTP or MPP+ analogues on mouse body temperature were studied. Of the analogues tested, 4-phenylpyridine (PPY) and 4-phenyl-1,2,3,6-tetrahydropyridine (PTP) given in single i.p. doses to mice caused marked hypothermia. Intracerebroventricular (i.c.v.) injection of PPY or PTP caused similar hypothermia. Pretreatment with clorgyline or (-)-deprenyl greatly prevented hypothermia induced by i.c.v. PPY, but hypothermia by i.c.v. PTP was prevented only by (-)-deprenyl. These results indicate that, in order to cause central hypothermia, PTP does not seem to require metabolism to PPY and both analogues per se may cause hypothermia.