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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 pituitary dopamine D2-receptors with a high affinity (Kd = 0.39 nM). In reserpinized rats, terguride at 0.03 mg/kg, p.o. significantly reduced the serum prolactin (PRL) level. The PRL lowering effect and the effective dose were longer lasting and about 30 times lower than those of bromocriptine, respectively. In rats bearing estrogen-induced pituitary prolactinoma, chronic terguride induced shrinkage of the prolactinoma as well as reduction of the high serum PRL level. In lactating rats, terguride (1.0 mg/kg, s.c.) reduced milk production in the mammary gland, whereas bromocriptine showed no significant effect up to 10 mg/kg, s.c. Terguride (10 mg/kg, p.o.) did not induce any stereotypy and hypermotility in reserpinized rats, while bromocriptine induced both stereotypy 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, bromocriptine induced both emesis and PRL-lowering at almost the same dose, whereas emesis-inducing doses of terguride were about 100 times higher than the PRL-lowering dose. These results suggest that terguride as a dopamine D2-agonist is a potent inhibitor of PRL secretion with less neurotropic side effects compared to bromocriptine, and thus a useful drug for the treatment of galactorrhea and hyperprolactinemia including prolactinoma.

Terguride as a New Anti-Hyperprolactinemic Agent: Characterization in Rats and Dogs in Comparison with Bromocriptine