Opiate-like effects of norlaudanosolinecarboxylic acids on the hypothalamic-pituitary-gonadal axis

Abstract

Norlaudanosolinecarboxylic acid (NLCA), a condensation product of dopamine and 3, 4-dihydroxyphenylpyruvic acid, has been found to exhibit opiate-like effects both in vitro and in vivo. The ability of NLCA to displace [ 3H] naloxone was measured in the presence and absence of 100 mM NaCI (IC 50 values = 2 × 10 −5M and 7.8 × 10 −7 M respectively). This large “Na + shift” suggested that NLCA was a relatively pure opiate agonist. Two analogs of NLCA, 3'- O-methyl NLCA (MNLCA) and 3', 4'-deoxy-NLCA (DNLCA), that have been shown to accumulate during L-dopa chemotherapy of Parkinsonism and phenylketonuria, respectively, also behaved as opiate agonists, but the concentrations required were higher than for NLCA. In addition, NLCA, like many opiates, decreased serum luteinizing hormone (LH) levels by approximately 50 per cent in both castrated and normal rats, 1–2 hr after its subcutaneous administration. Similarly, in normal males, serum testosterone levels were markedly depressed (60 per cent) after treatment with NLCA. The NLCA-induced depression in serum LH was naloxone reversible.