EFFECTS OF QUINAGOLIDE (CV-205-502), A SELECTIVE D-2-AGONIST, ON VASCULAR REACTIVITY IN PATIENTS WITH A PROLACTIN-SECRETING ADENOMA

BACKGROUND Quinagolide (CV 205 502) is a dopamine D-2-receptor agonist which has proved effective in the treatment of prolactinomas, reducin g both serum PRL and tumour size. Some of its D-2-receptor effects are mediated via alpha-adrenoceptors, which have a major influence on the control of vascular tone. The aim of this study was to examine the In fluence of quinagolide on in-vivo dorsal hand vein vascular responses to noradrenaline in patients with a prolactinoma. DESIGN AND PATIENTS Seven female patients with prolactinomas (age 37 (28-46) years), intol erant of bromocriptine, were studied before and after 3 months treatme nt with quinagolide (0.75-1.5 mg/day). Patients were otherwise disease free, were taking no other medication, and had been on no other medic ation (including bromocriptine) for at least 3 months prior to enrolme nt into the study. MEASUREMENTS Vascular responses to locally infused noradrenaline were measured in dorsal hand veins using an established technique. PRL, oestradiol, FSH, LH, blood pressure and body mass inde x were also measured before and after 3 months treatment. RESULTS Quin agolide significantly reduced PRL in all 7 patients (1795 (696-4680) ( mean (range)) vs 488 (290-868) mU/l, P=0.001), with no effect on the o ther parameters, including mean arterial pressure (88 (2) vs 87 (4) mm Hg, P=0 6). Vascular reactivity to noradrenaline was significantly inc reased after 3 months therapy: log(10) dose estimated to cause 50% vas oconstriction (ED(50)) 1.37 (0.12) vs 0 85 (0.12) ng/min (P=0.003; a l ower ED(50) Indicates less noradrenaline is required to constrict the vein by 50%). CONCLUSIONS Vasoconstrictor responses to noradrenaline w ere increased in all patients after 3 months treatment with quinagolid e. Peripheral veins carry alpha-adrenoceptors analogous to those of sy stemic resistance vessels. If this increased vasoconstrictor response in patients with prolactinomas was occurring in hypophyseal vessels, i t would lead to reduced tumour blood supply. Quinagolide may therefore reduce tumour blood flow, which may be one factor responsible for its effectiveness in these patients.