Quinagolide hydrochloride (CV205-502 hydrochloride)

Spectrophotometric determination of clobetasol propionate, halobetasol propionate, quinagolide hydrochloride, through charge transfer complexation

Two spectrophotometric procedures are described for the determination of clobetasol propionate(I), halobetasol propionate(II) (corticosteroids) and quinagolide hydrochloride(III) (prolactin inhibitor). For corticosteroid drugs, the procedures are based on the formation of phenyl hydrazones of the corticosteroids which are subsequently subjected to charge transfer complexation reaction with either 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as pi-acceptor or with iodine as sigma-acceptor. Prolactin inhibitor was reacted directly with the previous reagents. The molar ratios of the reactants were established and the experimental conditions were studied giving maximum absorption at 588 and 290 nm with DDQ and iodine methods, respectively for the three drugs. The concentration ranges were 20-150,50-300, and 20-80 microg ml(-1) in DDQ method for (I), (II), and (III), respectively and 13-20,15-40, and 8-32 microg ml(-1) in iodine method for (I), (II) and (III), respectively.

Plasma progesterone, oestradiol-17β and total oestrogen profiles in relation to oestrous behaviour during induced ovulation in Murrah buffalo heifers

The objectives of this study were to establish the characteristics of oestrous behaviour in Ovsynch (induction of ovulation through administration of GnRH-PGF2-GnRH in a systemic manner on 0, seventh and ninth day respectively) and Ovsynch plus Norprolac (Quinagolide hydrochloride – an inhibitor of prolactin secretion) treated Murrah buffalo heifers and to determine the relationships between this behaviour and the plasma concentrations of oestradiol-17β (E2), total oestrogen, and progesterone. Oestrus was detected by visual observations of oestrus signs, per rectal examination of genitalia and bull parading thrice a day during treatment period. Among all the symptoms, it was observed that bull mounting of heifers in oestrus was highest. Examination of genital tracts per rectum revealed that the cervix was relaxed, uterus was turgid and ovaries had palpable follicle in animals with oestrus. The peak concentrations of E2 (10.81 ± 0.62 pg/ml) and total oestrogen (17.11 ± 1.21 pg/ml) occurred at 9.45 ± 0.85 and 9.64 ± 0.93 h after second GnRH administration, respectively, in Ovsynch treated animals. However, the peak levels of E2 (20.02 ± 2.87 pg/ml) and total oestrogen (32.71 ± 3.15 pg/ml) occurred at 10.18 ± 0.50 and 10.36 ± 0.75 h after second GnRH administration, respectively, in Ovsynch plus Norprolac treated animals. Plasma progesterone concentration was basal (0.20 ± 0.001 ng/ml) during the peri-oestrus period. The plasma progesterone concentration was the lowest on the day of oestrus and increased to register a peak on day 13 ± 2 of the cycle. Oestrous behaviour was positively correlated with the peak concentration of E2 (p < 0.001) and total oestrogen (p < 0.001) during the peri-oestrus period. Inhibition of prolactin by Norprolac administration significantly increased the concentration of E2 and total oestrogen during oestrus in buffaloes in comparison to those recorded in animals subjected to Ovsynch protocol alone. In conclusion, our results suggest that the peak concentrations of E2 and total oestrogen and mean level of E2 and total oestrogen during the peri-oestrus period are the important factors contributing the behavioural manifestation of oestrus in buffalo cows.

Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells

Int J Mol Sci.2022 Feb 4;23(3):1775.PMID:35163699DOI: 10.3390/ijms23031775.

Endometrial mesenchymal stromal cells (E-MSCs) extensively contribute to the establishment and progression of endometrial ectopic lesions through formation of the stromal vascular tissue, and support to its growth and vascularization. As E-MSCs lack oestrogen receptors, endometriosis eradication cannot be achieved by hormone-based pharmacological approaches. Quinagolide is a non-ergot-derived dopamine receptor 2 agonist reported to display therapeutic effects in in vivo models of endometriosis. In the present study, we isolated E-MSCs from eutopic endometrial tissue and from ovarian and peritoneal endometriotic lesions, and we tested the effect of quinagolide on their proliferation and matrix invasion ability. Moreover, the effect of quinagolide on E-MSC endothelial differentiation was assessed in an endothelial co-culture model of angiogenesis. E-MSC lines expressed dopamine receptor 2, with higher expression in ectopic than eutopic ones. Quinagolide inhibited the invasive properties of E-MSCs, but not their proliferation, and limited their endothelial differentiation. The abrogation of the observed effects by spiperone, a dopamine receptor antagonist, confirmed specific dopamine receptor activation. At variance, no involvement of VEGFR2 inhibition was observed. Moreover, dopamine receptor 2 activation led to downregulation of AKT and its phosphorylation. Of interest, several effects were more prominent on ectopic E-MSCs with respect to eutopic lines. Together with the reported effects on endometrial and endothelial cells, the observed inhibition of E-MSCs may increase the rationale for quinagolide in endometriosis treatment.

Quinagolide--a valuable treatment option for hyperprolactinaemia

Eur J Endocrinol.2006 Feb;154(2):187-95.PMID:16452531DOI: 10.1530/eje.1.02075.

Hyperprolactinaemia is characterised by gonadal dysfunction, including infertility and reduced libido and, if left untreated, is associated with an increased risk of long-term complications, such as osteoporosis. The first-line therapy for patients with hyperprolactinaemia is pharmacological intervention with a dopamine agonist. Currently, there are three dopamine agonists available for hyperprolactinaemia therapy: bromocriptine, quinagolide and cabergoline. Bromocriptine has a long history of use; however, a range of 5-18% of patients are reported to show bromocriptine resistance, with only partial lowering of plasma prolactin levels and an absence of tumour shrinkage. The newer dopamine agonists, quinagolide and cabergoline, offer improved efficacy over bromocriptine, with a lower incidence of adverse events. Quinagolide and cabergoline have also demonstrated efficacy in many patients intolerant or resistant to bromocriptine. Thus, the selection of dopamine agonists available provides more than one option for pharmacological intervention of hyperprolactinaemia. This review discusses the clinical use of quinagolide in comparison to other dopamine agonists for hyperprolactinaemia therapy. Quinagolide may improve patient compliance to treatment owing to its reduced side effect profile, simple and rapid titration over just 7 days, once-daily dosing regimen and easy to use starter pack (available in some countries). Quinagolide offers an additional benefit for patients wishing to become pregnant, as it can be used until the point of confirmation of pregnancy. Therefore, as a well tolerated and effective therapy, with a simple dosing regimen, quinagolide should be considered as a first-line therapy in the treatment of hyperprolactinaemia.

The Non-Ergot Derived Dopamine Agonist Quinagolide as an Anti-Endometriotic Agent

Gynecol Obstet Invest.2017;82(6):527-532.PMID:27883998DOI: 10.1159/000452796.

Aim: The study aimed to investigate the efficacy of a dopamine agonist, quinagolide, on experimentally induced endometriosis in a rat model. Methods: Twenty female Wistar rats were used in this experiment. Endometriosis was surgically induced by transplantation of autologous endometrial tissue. A second laparotomy was performed 4 weeks after the first one to assess the pre-treatment implant volumes, and peritoneal lavage with saline solution was performed to assess the peritoneal cytokine levels. Rats were randomized to treatment with quinagolide or saline. At the end of the treatment period, a third laparotomy was performed to compare pre- and post-treatment implant volumes and cytokine levels within the groups. Implants were excised to compare glandular tissue (GT) and stromal tissue (ST) scores between the groups. Results: In the quinagolide group, post-treatment volume was statistically significantly reduced compared with pre-treatment volume (p = 0.01). There were significant decreases in interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels in peritoneal fluid samples in quinagolide-treated rats when compared to pre-treatment levels (p = 0.03 and p < 0.01). Histopathologically, both GT and ST scores were significantly lower in the quinagolide group compared to the control group (p = 0.01 and p = 0.02). Conclusions: Quinagolide caused a significant regression in endometriotic implants and it also significantly reduced the levels of IL-6 and VEGF in peritoneal fluid.