TERGURIDE AS A NEW ANTI-HYPERPROLACTINEMIC AGENT - CHARACTERIZATION IN RATS AND DOGS IN COMPARISON WITH BROMOCRIPTINE

Terguride, a derivative of the ergot alkaloid, was characterized as a new anti-hyperprolactinemic agent in rats and dogs in comparison with bromocriptine. Terguride was found to bind selectively to the pituitar y dopamine D-2-receptors with a high affinity (K-d=0.39 nM). In reserp inized rats, terguride at 0.03 mg/kg, p.o. significantly reduced the s erum prolactin (PRL) level. The PRL lowering effect and the effective dose were longer lasting and about 30 times lower than those of bromoc riptine, respectively. In rats bearing estrogen-induced pituitary prol actinoma, chronic terguride induced shrinkage of the prolactinoma as w ell as reduction of the high serum PRL level. In lactating rats, tergu ride (1.0 mg/kg, s.c.) reduced milk production in the mammary gland, w hereas bromocriptine showed no significant effect up to 10 mg/kg, s.c. Terguride (10 mg/kg, p.o.) did not induce any stereotypy and hypermot ility in reserpinized rats, while bromocriptine induced both stereotyp y and hypermotility significantly at 10 mg/kg, p.o. In dogs, terguride , like bromocriptine, reduced the serum PRL level, but did not affect the serum levels of growth hormone and luteinizing hormone. In dogs, b romocriptine induced both emesis and PRL-lowering at almost the same d ose, whereas emesis-inducing doses of terguride were about 100 times h igher than the PRL-lowering dose. These results suggest that terguride as a dopamine D-2-agonist is a potent inhibitor of PRL secretion with less neurotropic side effects compared to bromocriptine, and thus a u seful drug for the treatment of galactorrhea and hyperprolactinemia in cluding prolactinoma.