Treatment of prolactinoma patients with the new non-ergot dopamine agonist roxindol: first results

Abstract

We studied the effects of the new non-ergot D2-dopamine agonist roxindol for the treatment of human prolactinomas. Roxindol is a non-ergot drug with additional 5-hydroxytryptamine type 1 A agonist and serotonin reuptake inhibitory activity. Ten patients with prolactin-secreting pituitary adenomas received roxindol three times daily at a dosage of 7.5-30 mg/day for at least 4 weeks according to a prospective protocol. All patients but one had received oral bromocriptine previously without normalization of prolactin levels. Serum prolactin profiles were analyzed once a week during the first month of therapy and at 4-week intervals thereafter. Mean baseline serum prolactin was suppressed from 23,000 +/- 13,600 mU/l (range 1500-141,000 mU/l; 20 mU/l = 1 microgram/l) by 37 +/- 11% after 1 week, by 49 +/- 9% after 4 weeks, and by 65 +/- 11% (n = 8) after 24 weeks of treatment. Serum prolactin was normalized in two patients. A tumor volume reduction of 20-25% was obtained in two subjects. Compared with previous treatment with oral bromocriptine the decrease in serum prolactin was comparable. In contrast, tolerance of roxindol was superior in five of seven patients with major side effects with bromocriptine, including three subjects who had discontinued bromocriptine because of adverse reactions. Four subjects spontaneously reported improvement of psychological and physical performance. One patient had a transient increase of serum transaminases. Thus, for the first time we could show a suppressive effect of roxindol on prolactin secretion in human prolactinomas. Due to its good tolerance roxindol may provide a useful alternative to bromocriptine.

Robust, highly active, and stable supported Co(ii) nanoparticles on magnetic cellulose nanofiber-functionalized for the multi-component reactions of piperidines and alcohol oxidation

“…Aer the temperature studies, it was observed that 40 C was the most suitable temperature for this reaction. Increasing the temperature above 40 C did not show a signicant improvement but when the temperature reached 60 C, the product efficiency decreased (Table 1, entries [13][14][15][16]. Various piperidine derivatives were successfully prepared from the reaction of benzaldehyde and aniline derivatives, and ethyl/methyl acetoacetate.…”

“…Among the nitrogenous cyclic compounds, piperidines and their derivatives have shown impressive biological activity, such as antihypertensive, 5 antibacterial, 6 anticonvulsant, anti inflammatory agents, 7 farnesyltransferase inhibitors, 8 norepinephrine reuptake inhibitor, 9 antipsychotic agents, 10 and antidepressant. 11 In addition, piperidine derivatives act as an important group of therapeutic agents in the treatment of Parkinson's disease, 12 prolactinoma, 13 schizophrenia, 14 influenza infection, 15 cancer metastasis, 16 viral infections including AIDS, 17 obesity, and diabetes, 18 and also play key roles in many disease processes ( Scheme 1 ). 19 Due to the importance of these heterocyclic compounds in terms of the biological and medicinal properties, the introduction of a better and more efficient method for the preparation of piperidine derivatives is in demand.…”

Pituitary Prolactin-Secreting Tumor Formation: Recent Developments

“…A new dopaminergic agonist, CV 205-502, is also effective in prolactinoma patients previously intolerant to bromocriptine [10]. Recently, a nonergot DA agonist, roxindol, has also been reported to have a suppressive effect on prolactin secretion in human prolactinomas [11].…”

Estados hiperprolactinémicos.

“…El costo de los nuevos fármacos y la gran experiencia clínica con bromocriptina, hacen que esta siga desempeñando el principal papel dentro de los agonistas dopaminérgicos en el tratamiento de la hiperprolactinemia (38).…”