D-1 dopamine receptor stimulation elevates plasma prolactin levels

SKF 38393, a D-1 dopamine receptor agonist, produced dose-dependent elevations in plasma prolactin concentrations. Following the administration of SCH 23390, a D-1 antagonist, plasma prolactin concentrations tended to decrease; and low doses of SCH 23390 completely prevented the SKF 38393-induced elevations in plasma prolactin. These observations suggest that D-1 receptor stimulation can promote prolactin secretion.     

纳洛酮通过加强压力反射抑制缺血性心律失常

目的研究纳洛酮(Nal)抗心律失常作用与其对压力反射敏感性(BRS)影响的关系.方法:以冠状动脉结扎法制备Sprague-Dewley大鼠急性心肌梗塞模型,心电图记录室性早搏(VE),室性心动过速(VT)和心室颤动(VF);静脉注射苯肾上腺素后同步记录的收缩压与心动周期变化的回归直线斜率(b)为BRS;TTC染色法评价梗死范围.结果:Nal 0.5 mg iv,小脑延髓池注射(ic)Nal 0.1mg和ic β-内啡肽(β-End)抗血清10 μL可抑制缺血性心律失常,心律失常积分为1.8±1.1(Nal iv)vs 3.8±2.1(生理盐水iv);1.7±1.5(Nal ic)vs 4.0±2.6(人工脑脊液ic)和1.7±1.6(β-End抗血清ic)vs4.1±2.0(血清ic)(P<0.05);并可加强BRS,BRS为4.2±1.8(Nal iv)vs 2.9±0.8(生理盐水iv);4.5±1.7(Nal ic)vs2.8±0.7(人工脑脊液ic)和4.4±1.1(β-End抗血清ic)vs3.0±0.9(血清ic)(P<0.05).BRS与心律失常积分呈负相关,r值分别为-0.69(Nal,iv);-0.72(Nal,ic)及-0.67(β-End抗血清.ic).P值均<0.05.结论:Nal通过拮抗中枢β-End及加强BRS起抗心律失常作用.     

Naloxone effects on serum growth hormone and prolactin in man

The urinary excretion of 4-hydroxy-3-methoxyphenyglycol was compared in a group of 23 depressive patients and 27 control subjects of similar age. There was no difference between patients and controls although female controls excreted less than males. After 6 weeks' treatment with 150 mg daily of amitriptyline there was no correlation between therapeutic response and pretreatment urinary excretion value.     

Naloxone suppresses feeding and drinking but not wheel running in rats

The effects of naloxone hydrochloride on food and water intake and number of wheel revolutions were measured in male rats. The administration of 10 mg/kg naloxone but not 1 mg/kg suppressed the 3-hr food and water intake in nondeprived rats. Naloxone injections (1 mg/kg or 10 mg/kg) were ineffective in altering the number of wheel revolutions in nondeprived or food deprived rats. These results support the interpretation that the suppressive effects of naloxone previously reported with deprived rats are evident in nondeprived rats and are specific to feeding and drinking.     

Naloxone antagonism of electrical stimulation induced tail erection in mice

Tail erection was induced by focal electrical stimulation of the mesencephalic central gray through chronically implanted electrodes in mice. The response was current intensity dependent. Pretreatment with naloxone (5 mg/kg IP), a specific narcotic antagonist, abolished tail erection produced by low electrical current. In contrast, the tail response elicited by higher current was only partially blocked by naloxone. The results suggest that electrical stimulation induces tail erection by releasing an endogenous opioid peptide from the mesencephalic central gray.     

Naloxone protein binding in adult and foetal plasma

Summary Binding of naloxone hydrochloride was determined at 37°C, by equilibrium dialysis against 0.067 M phosphate buffer, pH 7.4, in plasma obtained from 18 healthy adults, and 18 samples of umbilical cord venous (foetal) plasma. The percentage free fraction (% free) in plasma was independent of naloxone concentration (9 ng/ml to 2.5 µg/ml). Percent free naloxone in adult (x=54.0) was lower (p<0.01) than in foetal (x=61.5) plasma. In buffered solutions of purified HSA, %free naloxone (x=68.7) was independent of HSA concentration over the range 3.0 g/dl to 5.5 g/dl. Adult plasma concentrations of ₁-acid glycoprotein (₁-AGP) and -lipoprotein were higher (p<0.01) than foetal concentrations. Furthermore %free naloxone in foetal plasma decreased with the in-vitro addition of purified ₁-AGP. It is suggested that qualitative differences in adult and foetal albumin and quantitative differences in plasma levels of ₁-AGP and perhaps -lipoprotein are responsible for naloxone plasma binding differences between adults and the newborn.     

Increased plasma prolactin levels induced in rats by d-fenfluramine: relation to central serotonergic stimulation.

d-Fenfluramine (7.5 and 10 mg/kg i.p.) and quipazine (10 and 20 mg/kg i.p.) increased plasma prolactin levels in male rats. Metergoline (3 mg/kg p.o.) or p-chlorophenylalanine (100 mg/kg X 3, orally) pretreatment markedly blocked the prolactin-releasing effect of both d-fenfluramine and quipazine. This result suggests that the effect of these drugs on prolactin secretion could be mediated through a serotonergic mechanism. Brain serotonin may thus exert a stimulatory role on prolactin secretion in rats.     

Evidence for a differential interaction of buprenorphine with opiate receptor subtypes controlling prolactin secretion

We studied the effects of various doses of the opiate derivative buprenorphine on serum prolactin levels and whether these effects could be counteracted by pretreatment with the opiate receptor blocker naloxone. The administration of increasing doses of buprenorphine exerted a dual effect on serum prolactin levels. At low doses (3, 10 and 30 micrograms/kg) this agent increased serum prolactin levels. This effect disappeared with increasing doses (100 and 300 micrograms/kg), and at the highest doses (1000 and 3000 micrograms/kg) the levels of serum prolactin decreased. Naloxone (30 mg/kg) decreased serum prolactin levels and reversed both the stimulatory and the inhibitory action of buprenorphine. These data are compatible with the hypothesis that buprenorphine could interfere with two different, but inter-dependent receptors: at low doses the oripavine derivative could act at one receptor site to cause an increase of serum prolactin, whereas at higher doses it could interact with a second site of lower affinity that is responsible for the inhibition of prolactin secretion. When buprenorphine (at high doses) activates the lower affinity site, the interaction with this receptor counteracts and reverses the effects of the high affinity site. On the basis of this hypothesis, naloxone should block both receptors.     

Naloxone antagonizes a central histaminergic stimulation of corticosterone secretion in rats

The interaction of central opioid receptors with histaminergic stimulation of the hypothalamo-pituitary-adrenocortical axis, evaluated indirectly through corticosterone secretion, was investigated in conscious unstressed rats. To avoid any possible direct action on the adrenal cortex, all drugs were given intracerebroventricularly (i.c.v.). Histamine, 2-pyridylethylamine (PEA), a histamine H1-receptor agonist, and 4-methyl-histamine (MeHA) and dimaprit, the H2-receptor agonists, considerably increased the serum corticosterone levels 1 h after administration. Naloxone, an opioid receptor antagonist, almost abolished the corticosterone response to PEA and considerably reduced the responses to MeHA, dimaprit and histamine. The maximum inhibitory effects of naloxone on corticosterone responses induced by histamine and histamine agonists were comparable with those of the H1- and H2-receptor antagonists, mepyramine and cimetidine. These results strongly suggest that a major part of the histaminergic stimulation of the hypothalamo-pituitary-adrenal axis is mediated by central opioid receptors.     

Changed plasma prolactin levels after etoperidone and placebo

A neuroendocrinological study was carried out by evaluating plasma prolactin levels after etoperidone i.m. (100 mg) and placebo. Fourteen male inpatients (mean age: 35.36 +/- 11.7 years) with chronic schizophrenia were selected for the study, whose aim was to improve interpretation of the pharmacological activity of etoperidone. The results suggest that etoperidone plays the role of an atypical psychotropic drug since it does not affect prolactin levels. In addition, the drug is devoid of anticholinergic effects, which facilitates its prospective clinical use for medium-term and long-term therapy.     

Naloxone suppresses insulin-induced food intake in novel and familiar environments,but does not affect hypoglycemia

The opiate antagonist naloxone reduced the food intake induced in rats by acute injection of insulin. The suppression was most marked in the first hour after insulin injection. Insulin provoked less food intake when rats were tested in a novel environment compared with those tested in their home cage, but naloxone again significantly suppressed the intake in the first hour. Naloxone had no effect upon insulin-induced hypoglycemia.     

Cardiovascular and plasma prolactin responses to stereoisomers of phencyclidine

The effect of phencyclidine (PCP) and dextro- and levorotatory isomers of its derivatives 1-(1-phenylcyclo-hexyl)-3-methylpiperidine [(+)-PCMP and (-)-PCMP] (5 mg/kg, SC) on blood pressure (BP), heart rate (HR) and plasma prolactin (PRL) were examined. PCP and (+)-PCMP but not (-)-PCMP increased BP and HR and suppressed plasma PRL.     

Sublingual buprenorphine used postoperatively: ten hour plasma drug concentration analysis.

1 A 10 h study of plasma drug concentrations of the opiate buprenorphine after use was designed because a previous 3 h study had shown that peak plasma drug concentrations in some patients had not occurred by 3 h after the sublingual dose. 2 Fifteen postoperative patients were studied: at 3 h after a 0.3 mg intravenous dose five patients received a sublingual preparation of 0.4 mg of buprenorphine, five 0.8 mg of buprenorphine and five placebo. Plasma drug concentrations of buprenorphine were measured by specific radioimmuno-assay. 3 Plasma drug concentrations after sublingual buprenorphine were significantly higher than those in the placebo group by 1 h. They remained significantly higher over the succeeding nine hours. The mean time to peak plasma drug concentration was about 200 min in both the 0.4 mg and 0.8 mg groups (range 90-360 min). The plasma drug concentrations in the 0.8 mg group were approximately twice those in the 0.4 mg group; the ratio of the relative systemic availabilities was similarly 1.8:1. The absolute systemic availability was estimated at about 55% for both groups. Uptake of buprenorphine from the sublingual site was essentially complete by 5 h after the dose was given. 4 The implications for the timing of sublingual doses in clinical use are discussed.     

Determination of buprenorphine in plasma by liquid chromatography: application to heroin-dependent subjects

A rapid, sensitive, precise and accurate HPLC assay with UV detection was developed for the determination of buprenorphine (BN) in human plasma. This method involved a two-step extraction in the presence of clothiapine as internal standard. The compounds were chromatographied on a reversed-phase Spherisorb® C8 column with a mobile phase consisting of 0.06 M KH₂PO₄/Na₂HPO₄ pH 6.4–acetonitrile–triethylamine–Pic B5® (520:480:0.5:15, v/v) and detected at 214 nm. The recovery of BN was greater than 94% with an intra-day relative standard deviation ≤4.8% and an inter-day relative standard deviation ≤14.6% at any studied level. Studies of drug stability during sample storage at −20°C and at +4°C did not show any significative degradation of BN. This method was successfully applied to explore the overdose state of heroin-dependent subjects treated by high-dose BN.     

Remoxipride: pharmacokinetics and effect on plasma prolactin.

1. The pharmacokinetics of remoxipride, a new neuroleptic, were investigated in 15 healthy subjects after an intravenous infusion of 50 mg, an intramuscular injection of 100 mg and after administration of two immediate release capsules (A and B), each of 100 mg, in a cross-over study. The effect of the different remoxipride formulations on plasma prolactin concentrations was also studied. 2. The volume of distribution of remoxipride was 0.65 +/- 0.11 kg-1 (mean +/- s.d.). Total plasma clearance was 119 +/- 39 ml min-1, of which 31 +/- 13 ml min-1 was due to renal clearance. The absolute bioavailability after the i.m. and oral formulations was greater than 90%, indicating a small extent of first-pass metabolism. The mean elimination half-life was 4.8 +/- 1.4 h. The unbound fraction of remoxipride and the blood/plasma ratio were 0.19 +/- 0.03 and 0.64 +/- 0.06, respectively. 3. The transient increase in plasma prolactin was similar after all four remoxipride administrations and independent of the given dose.     

Effect of d- and l-amphetamine on rat plasma prolactin levels

Although d- and l-amphetamine had no effect on plasma prolactin levels in untreated male rats, both d- and l-amphetamine reversed the increase in plasma prolactin levels produced by reserpine and 5-hydroxytryptophan (5-HTP). Only d-amphetamine significantly reversed the effect of alpha-methylparatyrosine (AMPT) on plasma prolactin levels. This reversal is probably due to a direct or indirect dopamine agonist effect of amphetamine, rather than to an effect on norepinephrine. This conclusion is based on the finding that apomorphine, a direct-acting dopamine agonist, reversed the reserpine-induced increase in prolactin secretion, while clonidine, a direct-acting alpha-adrenergic agonist, potentiated the reserpine-induced stimulation of prolactin secretion. The effect of d-amphetamine on the increase in plasma prolactin levels produced by reserpine, 5-HTP, or AMPT was always greater than that of the l-isomer, suggesting that the d-isomer has a more profound effect on dopaminerelease or neuronal reuptake, or both, than l-amphetamine. Chronic administration of d-amphetamine prior to reserpine did not inhibit the ability of d-amphetamine to reverse the reserpine-induced increase in plasma prolactin. Chronic administration of AMPT did not enhance the ability of d-amphetamine to reverse the AMPT-induced increase in plasma prolactin.