Changes In Serum Prolactin Levels Research Articles

Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema.

Diabetic retinopathy (DR) and diabetic macular edema (DME) are potentially blinding, microvascular retinal diseases in people with diabetes mellitus. Preclinical studies support a protective role of the hormone prolactin (PRL) due to its ocular incorporation and conversion to vasoinhibins, a family of PRL fragments that inhibit ischemia-induced retinal angiogenesis and diabetes-derived retinal vasopermeability. Here, we describe the protocol of an ongoing clinical trial investigating a new therapy for DR and DME based on elevating the circulating levels of PRL with the prokinetic, dopamine D2 receptor blocker, levosulpiride. It is a prospective, randomized, double-blind, placebo-controlled trial enrolling male and female patients with type 2 diabetes having DME, non-proliferative DR (NPDR), proliferative DR (PDR) requiring vitrectomy, and DME plus standard intravitreal therapy with the antiangiogenic agent, ranibizumab. Patients are randomized to receive placebo (lactose pill, orally TID) or levosulpiride (75 mg/day orally TID) for 8 weeks (DME and NPDR), 1 week (the period before vitrectomy in PDR), or 12 weeks (DME plus ranibizumab). In all cases the study medication is taken on top of standard therapy for diabetes, blood pressure control, or other medical conditions. Primary endpoints in groups 1 and 2 (DME: placebo and levosulpiride), groups 3 and 4 (NPDR: placebo and levosulpiride), and groups 7 and 8 (DME plus ranibizumab: placebo and levosulpiride) are changes from baseline in visual acuity, retinal thickness assessed by optical coherence tomography, and retinal microvascular abnormalities evaluated by fundus biomicroscopy and fluorescein angiography. Changes in serum PRL levels and of PRL and vasoinhibins levels in the vitreous between groups 5 and 6 (PDR undergoing vitrectomy: placebo and levosulpiride) serve as proof of principle that PRL enters the eye to counteract disease progression. Secondary endpoints are changes during the follow-up of health and metabolic parameters (blood pressure, glycated hemoglobin, and serum levels of glucose and creatinine). A total of 120 patients are being recruited. This trial will provide important knowledge on the potential benefits and safety of elevating circulating and intraocular PRL levels with levosulpiride in patients with DR and DME. Ethics approval has been obtained from the Ethics Committees of the National University of Mexico (UNAM) and the Instituto Mexicano de Oftalmología, I.A.P. Dissemination will include submission to peer-reviewed scientific journals and presentation at congresses. Registered at www.ClinicalTrials.gov, ID: NCT03161652 on May 18, 2017.

Changes in serum prolactin level during intracytoplasmic sperm injection, and effect on clinical pregnancy rate: a prospective observational study

BackgroundTransient hyperprolactinemia was proven to adversely affect the outcome of IVF. We aimed to identify changes in serum prolactin levels in patients undergoing ICSI, and to evaluate the effect of these changes on the clinical pregnancy rate.MethodsA prospective observational study included 90 patients scheduled for ICSI cycles. In each case 4 serum samples were collected during the cycle (midluteal, before ovum pick up procedure (OPU), 2 h after OPU, and before embryo transfer). Serum prolactin level was determined by immunoassay each time.ResultsThe sample collected 2 h after OPU had a mean difference of 25.8 ± 2.8 ng/ml compared to the basal serum prolactin (p < 0.01). In comparison to other samples, this highlighted a significant hyperprolactinemia occurring after OPU, and resolving before embryo transfer. No statistically significant difference between the different serum prolactin samples amongst the pregnant and non pregnant patients. There was a significant positive pearson correlation between the prolactin levels before OPU, and the presence of higher quality embryos (r = 0.274, p = 0.019).ConclusionIn normoprolactinemic women transient hyperprolactinemia is identified in patients undergoing ICSI, and it doesn’t affect the clinical pregnancy rates. A positive correlation was identified between higher quality embryos, and serum prolactin level before OPU.Trial registrationClinicalTrials.gov Identifier: NCT02292953, First received: November 10, 2014.

Association of Serum Prolactin Concentrations with Renal Failure in Diabetic Patients

Abstract Background and aims: Diabetes is one of the causes of end-stage renal disease, so that about 70% of all diabetic patients have nephropathy. Prolactin is a hormone that is affected by diabetes but the interaction between diabetes and prolactin has not been understood properly. This study aimed to evaluate the relationship between changes in serum prolactin levels in diabetic patients with renal failure. Material and methods: In this study 223 individuals were participated and after assessment of inclusion/exclusion criteria 189 individuals were evaluated. Finally, the individuals were divided into three groups: Control (C), Diabetic (D), and Diabetic Nephropathy (DN). Blood samples were collected between 8.00 a.m. and 12.00 a.m. for measurement of prolactin levels and biochemical analysis. Results: The results showed that sodium, potassium, urea, creatinine and prolactin significantly increased in DN group compared to control individuals (P&lt; 0.001). The prolactin levels were significantly decreased in the group of patients with diabetes (P&lt; 0.001). Conclusion: The results of the current study indicated that serum prolactin level decreased in diabetes while it increased in diabetic nephropathy.

Prolactin modulates luteal activity in the short-nosed fruit bat, Cynopterus sphinx during delayed embryonic development

The aim of this study was to evaluate the role of prolactin as a modulator of luteal steroidogenesis during the period of delayed embryonic development in Cynopterus sphinx. A marked decline in circulating prolactin levels was noted during the months of November through December coinciding with the period of decreased serum progesterone and delayed embryonic development. The seasonal changes in serum prolactin levels correlated positively with circulating progesterone (P) level, but inversely with circulating melatonin level during first pregnancy showing delayed development in Cynopterus sphinx. The results also showed decreased expression of prolactin receptor-short form (PRL-RS) both in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. Bats treated in vivo with prolactin during the period of delayed development showed significant increase in serum progesterone and estradiol levels together with significant increase in the expression of PRL-RS, luteinizing hormone receptor (LH-R), steroidogenic acute receptor protein (STAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in the ovary. Prolactin stimulated ovarian angiogenesis (vascular endothelial growth factor) and cell survival (B-cell lymphoma 2) in vivo. Significant increases in ovarian progesterone production and the expression of prolactin-receptor, LH-R, STAR and 3β-HSD proteins were noted following the exposure of LH or prolactin in vitro during the delayed period. In conclusion, short-day associated increased melatonin level may be responsible for decreased prolactin release during November–December. The decline in prolactin level might play a role in suppressing P and estradiol-17β (E2) estradiol levels thereby causing delayed embryonic development in C. sphinx.

SERUM PROLACTIN LEVELS IN TYPE-II DIABETES MELLITUS WITH RETINOPATHY PATIENTS IN AND AROUND HYDERABAD

Background & Objectives: Diabetes is a disease of metabolic dysregulation. Hyperglycemia and oxidative stress play a role in the development of late diabetic complications. Increased retinal vasopermeability occurs early in diabetes and is crucial for the development of sight-threatening diabetic retinopathy. Serum prolactin is proteolytically processed to vasoinhibins that inhibit the excessive retinal vasopermeability related to diabetic retinopathy. The aim is to study the role of serum prolactin and lipid profile in the pathogenesis of retinopathy in type 2 diabetics and to correlate the changes in serum prolactin levels. Methods: A case control study was done with 90 patients divided into 3 groups (healthy controls, Type 2 Diabetes without retinopathy and Type 2 Diabetes with retinopathy) with inclusion and exclusion criteria. Fasting blood samples were collected and fasting plasma glucose, serum Prolactin were measured. Multiple comparisons between different groups were done using ANOVA test. Results: In the present study decreased serum prolactin levels were observed in patients of Type 2 Diabetes with retinopathy compared to Type 2 Diabetes without retinopathy and controls. Mean ± S.D of Fasting plasma glucose, was highest in Group 3. Mean ± S.D of serum prolactin (7.737 ± 2.63) was low in Group 3. Interpretations & Conclusion: The circulating levels of prolactin were decreased in patients with diabetic retinopathy due to glycosylation and were higher in diabetic patients without retinopathy and healthy controls. Increased prolactin levels influence the progression of retinopathy after its intraocular conversion to vasoinhibins which can reduce the pathological retinal vasopermeability in diabetes and increase in prolactin can be considered to have protective role in pathogenesis of diabetic retinopathy and also may be considered as a treatment option for retinopathy. Key words: Prolactin; Diabetic retinopathy; Vasoinhibins; Retinal vasopermeability.

English

The interpretation of prolactin results is difficult as race related reference intervals are scarce, especially in Nigerian women. Serum prolactin reference intervals were determined from 120 subjects. Subjects were randomly selected from antenatal clinics and general outpatient clinics in one private hospital and three government hospitals in Zaria, Northern Nigeria. They consisted of six groups made up of women that were A-non pregnant, B-first trimester of pregnancy, C-second trimester of pregnancy, D-third trimester of pregnancy, E-labour, and F-puerperium. Their blood samples were collected via venipuncture between 09.00 and 13.00 h after which they were centrifuged and the sera stored at -8°C for further analysis. The samples were analyzed at the Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Shika. Serum prolactin was determined with Prolactin quantitative test kits using the principle of solid phase enzyme-linked immunosorbent assay. The concentration of prolactin is proportional to the color intensity of the samples as measured spectrophotometrically at a wavelength of 450 nm. Informed consent and ethical clearance was obtained before commencement of the study. Results were presented as mean ± standard deviation (SD) and data analyzed using one-way analysis of variance, while post-hoc test was carried out. A level of significance of p<0.05 was considered statistically significant, while the reference range was defined as 95% confidence interval. Serum prolactin results showed a significant increase in pregnant women as compared to the non-pregnant, not lactating subjects (20.24±3.41 ng/ml; 95% Confidence Interval (CI): 18.84-21.65 ng/ml). There were also significant trimester related differences in serum prolactin with prolactin levels increasing during the first trimester though not significantly (29.84±5.08 ng/ml). A sharp increase was observed during the second trimester (96.09±18.82 ng/ml; 95% CI: 89.41 to 102.76 ng/ml). There was a further increase at the third trimester (171.11±32.92 ng/ml; 95% CI: 159.03-183.18 ng/ml), a peaking during labour (198.37±15.81 ng/ml; 95% CI: 186.22-210.52 ng/ml) with a significant decline during the first week of the puerperium (197.19±22.11 ng/ml; 95% CI: 183.83-210.55 ng/ml). Apparent changes in serum prolactin levels were similar to that of previous studies; although the ranges for all groups were observed to be narrower as compared to those of other studies. Key words: Serum prolactin, reference ranges, enzyme immunoassay, Zaria.

Relation between serum prolactin levels and antipsychotic response to risperidone in patients with schizophrenia

BackgroundHyperprolactinemia is commonly seen in patients with schizophrenia on risperidone. Dopamine receptor blockade plays a major role in risperidone induced hyperprolactinemia. However, limited studies are available with inconsistent results on antipsychotic response to risperidone and prolactin elevation. Therefore, we aimed to study the change in serum prolactin levels and response to risperidone and to test the association between DRD2 genetic variants and prolactin levels in schizophrenic patients treated with risperidone. MethodsA prospective study comprising of 102 patients with schizophrenia were recruited. Prolactin levels and Positive and Negative Syndrome Scale (PANSS) score were recorded at baseline and after four weeks of risperidone treatment. Prolactin concentrations were measured by standard method Advia-Centaur® Chemiluminescence immuno assay method. Taq1A DRD2 genotyping was performed by qRT-PCR. ResultsThe mean±SD prolactin levels (ng/ml) were increased after four weeks of treatment in both responders (males 21.66±15.15 to 41.63±18.73; p<0.01 females 51.92±40.89 to 122.35±52.16; p<0.01) and non-responders group (males 23.89±14.85 to 37.45±13.5; p<0.01 females 39.25±26.94 to 91.13±54.31; p<0.01). Patients with increased prolactin concentration were 4.6 fold higher in responders (OR 4.60; 95%CI 1.376-15.389; p-value 0.01) compared to non-responders. Ninety-six patients were genotyped for Taq1A DRD2 gene (AA=9, AG=46, GG=41) and found no association (p=0.6) between genetic variants and response to risperidone. ConclusionPatients were showing more than 20% increase in prolactin levels had a better chance of responding to risperidone therapy. Taq1A DRD2 gene did not show any association with prolactin elevation and response to risperidone.

Effect of the Addition of Aripiprazole on Hyperprolactinemia Associated With Risperidone Long-Acting Injection

We sought to assess the effect of the addition of a fixed dose of 5 mg daily of aripiprazole on hyperprolactinemia induced by risperidone long-acting injectable (RLAI) treatment in patients with chronic psychoses and the adverse events related to the addition of aripiprazole and its impact on the disease. This is an open uncontrolled clinical trial with 13 patients with a severe mental disorder (schizophrenia and other unspecified psychoses) treated with RLAI and with increased serum prolactin levels. Subjects received the addition of a fixed dose of 5 mg daily of aripiprazole for 3 months. The main efficacy outcome was the change in serum prolactin levels after 3 months of treatment. Twelve of the 13 patients showed a decrease in serum prolactin levels (81 ± 46 μg/L at baseline vs 42 ± 21 μg/L at month 1, P < 0.001, 52% mean reduction). In 2 patients, prolactin levels reverted normality. In 8 patients who continued treatment for 2 more months, the decrease in prolactin levels was maintained. Symptoms associated with hyperprolactinemia improved, and no worsening of the Clinical Global Impression Scale scores was observed. The adverse effects due to the addition of aripiprazole were mild and transient. The addition of aripiprazole 5 mg daily to RLAI was associated with a significant decrease in hyperprolactinemia levels and no major additional toxicity in patients with chronic psychosis.

Successful Treatment With Blonanserin for Drug-Induced Hyperprolactinemia in Chronic Schizophrenia Patients: A Six-Month Follow-Up of Two Cases

Successful Treatment With Blonanserin for Drug-Induced Hyperprolactinemia in Chronic Schizophrenia Patients: A Six-Month Follow-Up of Two Cases

Serum prolactin levels before and after galactography in patients with pathological nipple discharge.

Serum prolactin levels were determined in 25 women who underwent galactography on account of pathological nipple discharge. The test samples were obtained immediately before galactography as well as 5, 10, 15 and 30 minutes after. There was no significant change in serum prolactin levels following galactography. In 2 cases out of 25, the basal level of prolactin was well above normal while in 1 case it was below normal. Those three were cases of galactorrhea. The clinical aspect of pathological nipple discharge did not correlate with serum prolactin levels, and galactorrhea would appear to be compatible with serum prolactin levels below normal.

Prolactin Levels in Olanzapine Treatment Correlate With Positive Symptoms of Schizophrenia

This study was designed to investigate the relationship between the treatment effect of olanzapine and the serum prolactin level in schizophrenia and to investigate the factors that may act as predictors of response for olanzapine treatment. Sixty patients who met the DSM-IV criteria for schizophrenia were included in the study. None of the patients were drug-naive, and they were given olanzapine in a flexible dose of 10-30 mg/day for 3 months after a 7-day drug washout period. Serum prolactin levels were measured at baseline (after drug washout) and at months 1, 2, and 3 during olanzapine treatment. A psychiatrist performed monthly ratings of symptoms using the Positive and Negative Syndrome Scale Manual (PANSS Manual). The Generalized Estimating Equations-I was used for data correlation analysis. Data were gathered from July 2005 to July 2006. In general, the serum prolactin level was decreased in schizophrenia patients with olanzapine treatment, although the difference is not statistically significant (p = .974, p = .246, and p = .363 for the first, second, and third months, respectively). There was a close relationship between the improvement in positive symptoms and the change in serum prolactin levels before and after olanzapine treatment (p = .002). Moreover, the serum prolactin level also had a positive association with female gender (p = .008). The present study demonstrated no significant correlation between serum prolactin level, MAOA polymorphism, and DRD4 genotype. This finding suggests that the serum prolactin level may be a useful biological marker to predict the effectiveness of antipsychotics in schizophrenia.

Serum prolactin levels, plasma risperidone levels, polymorphism of cytochrome P450 2D6 and clinical response in patients with schizophrenia

The object of this study is to assess 1) the relationship between plasma antipsychotic drug concentration, serum prolactin levels and the clinical efficacy of risperidone, 2) the relationship between the CYP2D6 polymorphisms and metabolizing of risperidone and 3) the role of 9-hydroxyrisperidone in elevating prolactin levels. One-hundred and eighteen Chinese schizophrenia patients (40 males, 78 females, age 15-60 years) were given risperidone at dosages ranging from 2-8 mg/day for 8 weeks. Clinical efficacy was determined using the Brief Psychiatric Rating Scores (BPRS). Serum prolactin levels were assayed before and after the 8 week treatment and plasma risperidone and 9-hydroxyrisperidone levels were also measured at the end of the 8-week treatment. The results showed there was no significant correlation between the concentration of active moiety and clinical response. Risperidone treatment significantly increased serum prolactin levels. Furthermore, changes of prolactin levels were not correlated with the clinical response. For the risperidone/ 9-hydroxyrisperidone ratio, there was a statistically significant difference among the CYP2D6*1/*1, *1/*10, *10/*10 genotypes (Kruskal-Wallis test, p = 0.012). No significant differences were found in the concentration of 9-hydroxyrisperidone and active moiety among the genotypes. In addition, the concentration of 9-hydroxyrisperidone was not significantly correlated with the increase of serum prolactin. In conclusion, our study has, for the first time, produced evidence that in Chinese schizophrenic patients, the metabolism of risperidone is dependent on CYP2D6. Neither changes in serum prolactin levels nor plasma concentration of active moiety were significantly correlated with clinical efficacy of risperidone. 9-hydroxyrisperidone may not play a predominant role in elevating serum prolactin level.

Serum Prolactin Levels Among Outpatients With Major Depressive Disorder During the Acute Phase of Treatment With Fluoxetine

To determine changes in serum prolactin levels in outpatients with DSM-IV-diagnosed major depressive disorder (MDD) following a 12-week open-label trial of fluoxetine. 87 outpatients enrolled in the trial had serum prolactin levels determined at baseline and during their final visit (week 12 or discontinuation visit). In addition, serum testosterone levels were measured in 44 of the 46 men during these 2 visits. Hyperprolactinemia was defined as a serum prolactin level greater than 16.5 ng/mL or 18.9 ng/mL for men and women, respectively. The study was conducted from September 1997 to March 2002. Of 80 patients with normal prolactin levels at baseline, 10 (12.5%) developed hyper-prolactinemia following fluoxetine treatment. Specifically, 2 (4.5%) of 44 men and 8 (22.2%) of 36 women with normal prolactin levels at baseline developed hyperprolactinemia following treatment with fluoxetine (p = .0174 for between-gender difference). In addition, there was a significant increase in mean +/- SD serum prolactin levels following treatment with fluoxetine in all patients with normal baseline prolactin levels (6.4 +/- 3.4 to 10.0 +/- 7.0 ng/mL, p = .002). There were no significant changes from baseline in testosterone levels in men following fluoxetine treatment (448.4 +/- 139.6 to 439.5 +/- 142.1 ng/dL, p > .05; normal above 245 ng/dL), while none of the 44 men developed low testosterone levels following fluoxetine treatment. 4.5% of men and 22.2% of women with MDD developed new onset hyper-prolactinemia following fluoxetine treatment.

The relationship between prolactin response and clinical efficacy of risperidone in acute psychotic inpatients

Hyperprolactinemia can be induced by dopamine D2 receptor-binding drugs such as antipsychotic drugs. The author investigated the relationship between changes in prolactin (PRL) and clinical efficacy of risperidone. In this study, 27 acute psychotic inpatients completed a 12-week trial of risperidone. At baseline and at 2, 4, 8, and 12 weeks after beginning medication, the author measured PRL, assessed hyperprolactinemia-related symptoms, and administered the Brief Psychotic Rating Scale (BPRS). Risperidone treatment significantly elevated serum PRL level (range: 26.9 ng/ml–320.0 ng/ml). The increases of PRL in females were higher than males. The changes in serum PRL levels were not significantly correlated with the improvements in total BPRS scores. PRL-related symptoms such as irregular menstruation, galactorrhea, or erectile dysfunction occurred in nine subjects (7 females and 2 males) whose serum PRL levels increase very highly after 2 weeks of risperidone. In conclusion, our study suggests that the changes in serum PRL levels were not significantly correlated with clinical efficacy of risperidone.

Switching Female Schizophrenic Patients to Quetiapine from Conventional Antipsychotic Drugs: Effects on Hyperprolactinemia

Conventional antipsychotic medications are associated with elevated prolactin levels, resulting in hyperprolactinemia and a number of unwanted side effects. Several atypical antipsychotics, on the other hand, are less likely to evoke hyperprolactinemia. The aim of this study was to investigate the prevalence of hyperprolactinemia induced by conventional antipsychotic drugs, examine changes in serum prolactin levels and psychiatric symptoms after switching to quetiapine, and identify the relevant characteristics of patients who may be suitable to switch to quetiapine. Sixty-nine of 74 consecutive female patients who had received conventional antipsychotic drugs were initially included in the study. Of these, 49 (71 %) patients suffered from hyperprolactinemia, of which a further 25 were subsequently switched to quetiapine. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS), and serum prolactin levels were measured just before and at 4 and 8 weeks after switching. Eight of the 25 (32 %) "switch" patients dropped out due to psychotic exacerbation during the 8 weeks. In the remaining 17 (68 %) patients, serum prolactin levels were significantly decreased without any significant change in PANSS scores after switching. The 17 patients who completed the switch had previously demonstrated significantly lower positive symptom scores compared to the 8 dropout patients. The present findings suggest that 71 % of female patients receiving conventional antipsychotic drugs may suffer from hyperprolactinemia and that approximately two-thirds of patients can be switched to quetiapine, resulting in an improvement in hyperprolactinemia. The main characteristic of the switched patients may be fewer positive symptoms.

Molting in the Djungarian hamster (Phodopus sungorus Pallas): Seasonal or continuous process?

After transfer into a short daylight regimen, the brownish summer pelage of the Djungarian hamster (Phodopus sungorus) changes into the whitish winter phenotype. Although changes in serum prolactin levels are identified as the initiating hormonal signal, morphological data about molting in that species are sparse. The aim of this study was to characterize in detail the summer and winter pelage of the Djungarian hamster and to analyze the alterations in the skin and pelage induced by photoperiodic changes. The main difference between summer and winter hair types is the pattern of pigmentation. In contrast to other mammalian species showing seasonal changes, the winter coat of the Djungarian hamster is not characterized by an increase in hair density. Molting patches were observed at all times, even in the winter coat, showing that the light regimen does not control the process of molting itself but the pattern of pigmentation and eventually the loss of hair during the single molting wave.

Effects of 5-day styrene inhalation on serum prolactin and dopamine levels and on hypothalamic and striatal catecholamine concentrations in male rats.

In several studies a hypersecretion of the pituitary hormone prolactin (PRL) in styrene-exposed workers has been described. This should cause reproductive problems like oligomenorrhea, secondary amenorrhea and reduced fertility [Arfini et al. (1987) J Occup Med 29:826-830, Bergamaschi et al. (1996) Neurotoxicology 17:753-760, Mutti and Smargiassi (1998) Toxicol Ind Health 14:311-323]. Secretion of PRL is tonically inhibited by the catecholamine dopamine (DA), which is released from hypothalamic neurons. It has been suggested that the activity of the enzyme dopamine-beta-hydroxylase (DBH) in the serum is a peripheral marker of central dopaminergic function. A slight reduction of such enzymatic activity was observed in styrene-exposed workers, which was associated with hypersecretion of PRL. To further investigate the putative effects of styrene on PRL release, male rats were exposed to styrene vapors (645, 2150 and 6450 mg/m(3)) for 6 h/day on 5 consecutive days. Animals were killed either directly following the last exposure (immediate group) or after a recovery period of 24 h (recovery group). Serum PRL and DA levels were measured by radioimmunoassay. Concentrations of catecholamines and their metabolites in the striatum and mediobasal hypothalamus (MBH) were determined by high performance liquid chromatography with electrochemical detection. Neither in the immediate nor in the recovery group were any statistically significant changes of serum PRL levels observed. Likewise, concentrations of catecholamines and their metabolites in the striatum and MBH remained unaffected. We conclude from these data that styrene, even at very high concentrations, has no adverse effects on the neuroendocrine mechanisms regulating PRL release and DA levels in the brain. With the limitations inherent in any animal model, we suggest that our data indicate that styrene also has no adverse neuroendocrine effects in humans.

Sertindole: safety and tolerability profile

Sertindole is a novel generation or atypical antipsychotic drug that has recently been re-introduced to the market. The safety and tolerability profile of sertindole have demonstrated a positive benefit/risk ratio in clinical trials and post-marketing studies. The number of patients who experienced extrapyramidal symptoms (EPS) while taking sertindole in clinical trials was similar to that of patients on placebo, and significantly less than that of patients on haloperidol. The relative lack of EPS is probably the result of the drug's highly selective blockade of limbic dopamine D 2 receptors and its lack of effect on other dopamine D 2 receptors, but may be due to low occupancy at dopamine D 2 striatal receptors. Sertindole also has a high affinity for serotonin 5-HT 2 and f 1 receptors. It has been shown not to cause sedation and its propensity to cause anticholinergic side effects is low, probably due to its lack of antihistamine and antimuscarinic activity. Sertindole does not cause any clinically significant changes in serum prolactin levels. QT interval prolongation does occur in some patients. The sertindole mortality rate is comparable to that of both risperidone and olanzapine (1.46, 1.75 and 1.20, respectively). Overall, sertindole is a well-tolerated drug that does not cause EPS, sedation or hyperprolactinaemia.

Antiprolactin autoantibodies are associated with hyperprolactinemic status in men infected with human immunodeficiency virus.

High serum prolactin (PRL) levels and even hyperprolactinemia are a common finding in human immunodeficiency virus (HIV) infection. However, little is known regarding the mechanisms that may contribute to the rise of PRL. We measured serum PRL levels in 54 HIV-infected and 85 healthy age-matched men. The association between PRL levels among anti-PRL autoantibodies and other clinical variables in HIV-infected men was studied. We also evaluated the changes in serum PRL levels by chromatographic separation (affinity with protein G and gel filtration) after a 10-mg iv bolus of metoclopramide. HIV-infected men had higher serum PRL levels compared with healthy men. Sera from 9 of the 54 (16.7%)HIV-infected men were found to have hyperprolactinemia. Moreover, the anti-PRL autoantibody was present in four of nine (44.4%)HIV-infected men with hyperprolactinemia; it was also associated with hyperprolactinemic status. Serum total PRL levels were higher in HIV-infected men with anti-PRL autoantibodies than hyperprolactinemic HIV-infected men without anti-PRL autoantibodies; by contrast, free PRL levels were lower. In HIV-infected men with anti-PRL autoantibodies, gel filtration showed that big big PRL isoform was present as the predominant circulating form of PRL throughout each measurement after iv metoclopramide. By contrast, the predominant isoform of PRL in serum from healthy men and HIV-infected men who were anti-PRL autoantibody negative was little PRL. On the other hand, high serum total PRL levels were observed at each measurement throughout the metoclopramide test in HIV-infected men with anti-PRL autoantibodies; however, the serum free PRL levels were similar to those found in subjects without anti-PRL autoantibodies. These data demonstrated that anti-PRL autoantibodies are associated with hyperprolactinemic status in HIV-infected subjects, particularly in those with high serum PRL levels.

Participation of the opioid system in the regulation of prolactin secretion in androgenized rats: effect of ovarian steroids

We examined the role of the opioid system on the regulation of prolactin secretion in neonatally androgenized rats and evaluated the participation of ovarian steroids in this regulation. Androgenized rats exhibited an increase of prolactin secretion with higher serum circulating levels in the afternoon (1800) than in the morning (1000). The administration of the opioid antagonist naloxone (2 mg/kg, 30 min before decapitation) reduced serum prolactin levels in both groups. To identify the opioid receptor subtypes involved in this regulation, opioid agonists were administered i.c.v. 15 min before the decapitation (1000). The μ-opioid receptor agonist DAMGO ([ d-Ala 2, NMe-Phe 4, Gly 5-ol]-enkephalin) caused a significant increase in serum prolactin concentration. The selective κ-opioid receptor agonist U-50, 488H ( trans-(±)-3,4-dichloro- N-[2(1-pyrrolidinyl)-cyclohexyl]-benzene acetamide methane sulfonate salt) induced a small but significant increase in serum prolactin levels but no effect was observed after administration of the δ-opioid agonist DPDPE ([ d-Pen 2, d-Pen 5]-enkephalin). The role of oestradiol and the opioid system in the continuous secretion of prolactin was also study. Chronic gonadectomy (3–4 weeks) reduced serum prolactin concentrations measured at 1000 but the administration of naloxone had no effect. Three days of oestrogen treatment (2 μg/rat in oil) restored serum prolactin levels compared with ovariectomized animals and this effect was abolished by naloxone treatment. Interestingly, acute ovariectomy or administration of tamoxifen to intact androgenized rats did not prevent the continuous secretion of prolactin observed in these animals and naloxone treatment reduced serum prolactin levels in both groups of rats. We also examine the participation of adrenal progesterone and the endogenous opioid peptides on the regulation of prolactin levels in androgenized rats. After adrenalectomy, no changes in serum prolactin levels (1000) were observed compared with the control animal and naloxone treatment significantly reduced circulating prolactin levels. Progesterone treatment to intact androgenized rats significantly increased prolactin levels and the administration of naloxone blocked the stimulatory effect of the steroid. These results suggest that the opioid system play a role in the regulation of prolactin secretion in androgenized rats modulated by the persistence of oestrogen action. Moreover, the presence or absence of progesterone did not modify the regulation of prolactin secretion by the opioids. The μ- and κ-opioid receptor subtypes are the ones involved in the modulation of pituitary prolactin secretion.