piperidines and Hyperprolactinemia

The objective of this study was to evaluate the efficacy and tolerability of blonanserin for the treatment of Korean patients with schizophrenia using a double-blind risperidone-compared design.. Patients aged 18 to 65 years with schizophrenia were randomly assigned to blonanserin or risperidone treatment for 8 weeks. The efficacy was assessed using the mean change in Positive and Negative Syndrome Scale score total scores from baseline to week 8. Safety assessments included monitoring of vital signs, a physical examination, laboratory tests, and adverse events.. Of 206 randomly enrolled patients, 103 receiving blonanserin and 103 receiving risperidone were included in the analysis. In this study, noninferiority between blonanserin and risperidone was demonstrated. The mean change in the Positive and Negative Syndrome Scale total score at the final evaluation time point was -23.48 +/- 19.73 for the blonanserin group and -25.40 +/- 18.38 for the risperidone group. Adverse events, which occurred less frequently in the blonanserin than in the risperidone group, included dysarthria (P = 0.0288), dizziness (P = 0.0139), increased alanine aminotransferase and aspartate aminotransferase (P = 0.0095 and P = 0.0032, respectively), and increased level blood prolactin (P = 0.0012). On the other hand, the adverse events that occurred more frequently in the blonanserin than in the risperidone group was hand tremor (P = 0.0006).. Blonanserin was effective in the treatment of Korean patients with schizophrenia compared with risperidone and was more tolerable with a better safety profile, particularly with respect to prolactin elevation. These findings suggest that blonanserin is useful in the treatment of schizophrenia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Piperazines; Piperidines; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Weight Gain; Young Adult

The availability of a new specific anti 5HT-2 compound, ritanserin (RTS), led us to further investigate the role of serotonin in controlling PRL secretion. The drug was administered to normoprolactinaemic subjects and to patients with differing hyperprolactinaemic conditions. While RTS failed to modify PRL levels in normoprolactinaemic subjects and in patients with PRL-secreting pituitary adenomas, a marked decrease in the hormone was obtained in patients with functional and puerperal hyperprolactinaemia. The lack of effect of RTS in PRL-secreting pituitary adenomas suggests that the reported suppression of PRL by other antiserotoninergic drugs, such as metergoline, is probably due to their concomitant dopaminergic activity.

Topics: Adenoma; Female; Follicular Phase; Humans; Hyperprolactinemia; Piperidines; Pituitary Neoplasms; Postpartum Period; Pregnancy; Prolactin; Ritanserin; Serotonin Antagonists; Single-Blind Method; Sulpiride

A series of benzoisoxazoleylpiperidine derivatives were synthesized by using the multi-target strategies and their potent affinities for dopamine (DA), serotonin (5-HT) and human histamine H

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Cognition; Dopamine; Drug Design; Humans; Hyperprolactinemia; Mice; Models, Animal; Movement; Piperidines; Protein Binding; Receptors, Histamine H3; Risperidone; Serotonin; Structure-Activity Relationship; Weight Gain

Topics: Adult; Antipsychotic Agents; Chronic Disease; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Male; Middle Aged; Piperazines; Piperidines; Prolactin; Schizophrenia

Dopaminergic stabilizers may be conceptualized as drugs with normalizing effects on dopamine-mediated behaviours and neurochemical events. (S)-(-)-OSU6162 (OSU6162) and ACR16 are two structurally related compounds ascribed such properties, principally because of their stabilizing effects on motor activity in rodents. Reports in the literature indicate possible partial D2 receptor agonist effects using various in vitro systems. This study aimed to measure D2 receptor antagonist and agonist effects of OSU6162 and ACR16 in vivo. To address this, we have studied the effects of both compounds on prolactin secretion in drug-naive and dopamine-depleted rats; dopamine depletion was induced by pretreatment with reserpine plus α-methyl-DL: -p-tyrosine. We find that OSU6162 and ACR16 both stimulate prolactin secretion in drug-naive rats with OSU6162 being considerably more potent and efficacious. Both compounds show a non-significant trend towards reversal of the increased secretion caused by dopamine depletion, whereas the D2 receptor antagonist haloperidol further increased prolactin secretion. Thus, this study suggests that OSU6162 and ACR16 act as D2 receptor antagonists under normal conditions in vivo, possibly with minor agonist effects in a state of dopamine depletion.

Topics: Animals; Aripiprazole; Dopamine; Dopamine Agonists; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Haloperidol; Hyperprolactinemia; Lactotrophs; Male; Methyltyrosines; Piperazines; Piperidines; Prolactin; Quinolones; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; Reserpine

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dopamine Antagonists; Female; Humans; Hyperprolactinemia; Piperazines; Piperidines; Quinolones; Schizophrenia

Topics: Antipsychotic Agents; Female; Humans; Hyperprolactinemia; Isoxazoles; Piperidines; Premenopause; Prolactin; Risperidone; Schizophrenia

The present investigation was aimed at comparing the influence of the partial dopamine (DA) receptor agonist (-)-3-PPP (preclamol) on prolactin release in acutely hyperprolactinemic but otherwise intact female rats and female rats subjected to chronic DA depletion. One group of animals received daily vehicle injections (controls) and another group daily reserpine (1 mg/kg) injections for a period of seven days. On the eighth day all animals were administered 10 mg/kg of reserpine in order to eliminate endogenous DA and elevate serum prolactin levels. In the control group (-)-3-PPP lowered serum prolactin levels only moderately. In contrast, in the chronically reserpinized female rats, a pronounced reduction of prolactin secretion was observed. It is suggested that this increase in intrinsic activity of (-)-3-PPP following chronic DA depletion reflects an enhanced responsiveness of hypophyseal DA receptors, possibly due to conformational changes in the receptor molecules. Our observations lend further support to the hypothesis that an inverse relationship exists between the intrinsic activity of a mixed agonist/antagonist and the degree of previous receptor occupancy.

Topics: Animals; Dopamine; Female; Hyperprolactinemia; Piperidines; Pituitary Gland; Prolactin; Rats; Rats, Inbred Strains; Receptors, Dopamine; Reserpine