Dl-threo-DOPS as a precursor of noradrenaline

Abstract

DL-threo-Dihydroxyphenylserine (DL-threo-DOPS) is a non-physiological precursor of noradrenaline (NA). The formation of NA from DL-threo-DOPS has been reported to occur in various mammalian tissue. Since NA deficiency is thought to be underlying mechanism in several neurological disorders, we studied the role of the DL-threo-DOPS as a precursor of NA. In rats treated with DL-threo-DOPS, heart NA levels increased in a dose-dependent manner with maximal effect obtained 1 h after intraperitoneal injection of the drug. However, no effect of DL-threo-DOPS on brain NA levels or DA metabolism was detected. The effect of DL-threo-DOPS on heart NA levels was completely inhibited in the presence of carbidopa and significantly enhanced in the presence of pargyline. Under these conditions, DL-threo-DOPS had no effect on brain catecholamines. Depletion of catecholamines was obtained by pretreatment with either alpha-methyl-p-tyrosine (AMPT), reserpine or FLA-63. DL-threo-DOPS increased NA levels in the heart but not in the brain. Finally, coadministration of DL-threo-DOPS with levodopa potentiated the effect of levodopa on brain DA metabolism. This effect was independent of peripheral dopa decarboxylase activity and was also shown in circling behaviour in rats with unilateral destruction of the nigrostriatal pathway. In rats, DL-threo-DOPS is an effective peripheral precursor of NA but the drug itself has no effect on brain catecholamines. DL-threo-DOPS may, however, enhance levodopa effects in the brain.