Influence of the dosing interval on prolactin release after remoxipride.

Movin-Osswald, Gunilla; Hammarlund‐Udenaes, Margareta; Bahr, C von; Eneroth, P.; Walton–Bowen, Karen

doi:10.1111/j.1365-2125.1995.tb04487.x

Cited by 9 publications

(16 citation statements)

References 38 publications

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“…In a pediatric population, clozapine was found to have prolactin-sparing effects similar to those in the adult population, whereas olanzapine had a significantly greater effect on prolactin release, albeit lower than that of haloperidol (Wudarsky et al, 1999). However, with the prolactin-sparing antipsychotics, this increase does not last until the next dose, and therefore, there is no cumulating prolactin elevation over time (Movin-Osswald et al, 1995;Turrone et al, 2002). Thus, although the central to peripheral ratio is probably one of the most important determinants of the prolactin effects of atypical antipsychotics in the clinical situation, it is not the only relevant factor.…”

Section: Discussionmentioning

confidence: 88%

“…The precise mechanism of this tolerance is not known, but there is no reason to believe that changes in the centralperipheral disposition contribute to it. Furthermore, it is also becoming clear that pharmacokinetic variables such as the rate of the rise of plasma levels and the transience of the high plasma levels are also relevant for prolactin elevation (Movin-Osswald et al, 1995). For example, although atypical antipsychotics such as quetiapine, clozapine, olanzapine, remoxipride, and ziprasidone are not associated with sustained prolactin elevation, each of these "prolactin-sparing" atypical antipsychotics is associated with a short-lasting transient prolactin increase immediately after the dose is administered (Crawford et al, 1997;Turrone et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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The Differential Effects of Atypical Antipsychotics on Prolactin Elevation Are Explained by Their Differential Blood-Brain Disposition: A Pharmacological Analysis in Rats

Kapur¹,

Langlois²,

Vinken³

et al. 2002

J Pharmacol Exp Ther

147

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All atypical antipsychotics avoid extrapyramidal side-effects yet differ in their propensity to cause other side-effects, like prolactin elevation. We proposed that the atypical antipsychotics with a propensity for prolactin elevation would show a higher pituitary versus striatal D2 receptor occupancy. To investigate this hypothesis, we tested four atypical antipsychotics, two that are commonly associated with prolactin elevation (amisulpride and risperidone) and two that are less frequently associated (quetiapine and olanzapine). In particular, we calculated their ED 50 values to increase plasma prolactin and block peripheral pituitary D2 receptors to their ED 50 values to antagonize apomorphine-induced stereotypy and occupy central striatal D2 receptors. All antipsychotics dose dependently increased prolactin levels and antagonized apomorphine-induced stereotypy. However, the central to peripheral potency (ED 50 for apomorphine antagonism to ED 50 for prolactin elevation) differed remarkably across these drugs: amisulpride (21764), risperidone (14), quetiapine (10), and olanzapine (1.7). Compounds displaying a higher peripheral potency brought about higher prolactin levels for a given level of functional central antagonism. This dissociation between central and peripheral effects was explained by the differential occupancy of D2 receptors in the striatum versus in the pituitary [ratio of striatal/pituitary ED 50 values (milligram per kilogram) for D2 occupancy): amisulpride (17/0.026 ϭ 654), risperidone (0.89/0.081 ϭ 14), quetiapine (24/4.1 ϭ 6), olanzapine (0.30/0.43 ϭ 0.7). These results indicate that dissociation between central and peripheral D2 receptor occupancy is a major determinant of the degree of prolactin elevation observed at therapeutic doses.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

The Differential Effects of Atypical Antipsychotics on Prolactin Elevation Are Explained by Their Differential Blood-Brain Disposition: A Pharmacological Analysis in Rats

Kapur¹,

Langlois²,

Vinken³

et al. 2002

J Pharmacol Exp Ther

147

View full text Add to dashboard Cite

show abstract

“…Furthermore, baseline variations in plasma prolactin concentrations were investigated [148]. Also, the prolactin response was measured following double low dosing of remoxipride at different time intervals to get information on the synthesis of prolactin in the pituitary lactotrophs [149,150]. The final PK-PD model consisted of 1) a pharmacokinetic model for plasma and unbound brain remoxipride concentrations, 2) a pool model for prolactin synthesis and storage, and its release into- and elimination from plasma, 3) a positive feedback of prolactin plasma concentrations on prolactin synthesis, and 4) the brain unbound concentrations of remoxipride for the inhibition of the D2 receptor, and resulting stimulation of prolactin release into plasma.…”

Section: Resultsmentioning

confidence: 99%

“…Human data on remoxipride and prolactin plasma concentrations were used, being obtained following double intravenous administration of remoxipride at different time intervals [149]. The translational PK-PD model successfully predicted the remoxipride plasma kinetics in humans (Figure 8) as well as system prolactin response in humans, indicating that positive feedback on prolactin synthesis and allometric scaling thereof could be a new feature in describing complex homeostatic processes [147].…”

Section: Resultsmentioning

confidence: 99%

The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

Lange

2013

Fluids Barriers CNS

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Despite enormous advances in CNS research, CNS disorders remain the world’s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies.Following dosing, not only the chemical properties of the drug and blood–brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. The rate and extent of all these processes are regulated dynamically, and thus condition dependent. Therefore, heterogenious conditions such as species, gender, genetic background, tissue, age, diet, disease, drug treatment etc., result in considerable inter-individual and intra-individual variation, often encountered in CNS drug therapy.For effective therapy, drugs should access the CNS “at the right place, at the right time, and at the right concentration”. To improve CNS therapies and drug development, details of inter-species and inter-condition variations are needed to enable target site pharmacokinetics and associated CNS effects to be translated between species and between disease states. Specifically, such studies need to include information about unbound drug concentrations which drive the effects. To date the only technique that can obtain unbound drug concentrations in brain is microdialysis. This (minimally) invasive technique cannot be readily applied to humans, and we need to rely on translational approaches to predict human brain distribution, target site kinetics, and therapeutic effects of CNS drugs.In this review the term “Mastermind approach” is introduced, for strategic and systematic CNS drug research using advanced preclinical experimental designs and mathematical modeling. In this way, knowledge can be obtained about the contributions and variability of individual processes on the causal path between drug dosing and CNS effect in animals that can be translated to the human situation. On the basis of a few advanced preclinical microdialysis based investigations it will be shown that the “Mastermind approach” has a high potential for the prediction of human CNS drug effects.

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“…Movin-Osswald and Hammarlund-Udenaes [19] showed, using the D2 dopamine receptor blocker remoxipride in two consecutive doses at several time intervals, that the prolactin pool is fully restored after 24 to 48 hours, and that the refractory period for a second prolactin release after remoxipride, similar to the first prolactin release, was 24 hours for most of the subjects [20].…”

Section: Discussionmentioning

confidence: 99%

Relationship between prolactin responses to ECT and dopaminergic and serotonergic responsivity in depressed patients

Markianos

Hatzimanolis

Lykouras

2002

European Archives of Psychiatry and Clinical Neurosciences

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The prolactin (PRL) increases in plasma, induced by the electrical stimulus during electroconvulsive therapy (ECT), is a consistent finding that can be studied in order to obtain information about its actions on the brain neurotransmitter systems, the most probable candidates being the serotonergic and the dopaminergic system. Central serotonergic and dopaminergic responsivity may also be assessed using neuroendocrine challenge tests. In this study, we measured the PRL responses during the first ECT of a therapeutic course in 15 male depressive patients, of mean age 49.2 +/- 14.5 (range 22 to 68 years), and score in the HDRS of 29 +/- 8 (range 18 to 43 points). Before the ECT course, we assessed the central serotonergic and dopaminergic responsivities, by measuring the PRL responses to the administration of the serotonin uptake inhibitor clomipramine (CMI) intravenously, and, two days later, the PRL responses dopamine receptor blocker haloperidol (HAL), administered intramuscularly. The CMI and HAL tests were also performed in 15 healthy male subjects. The PRL responses to CMI of the patients were blunted compared to healthy controls, while the PRL responses to HAL were not significantly different from controls. Searching for correlations among the maximal PRL responses to the three stimuli in the patient's group, we found that the PRL responses to ECT were significantly correlated to the PRL responses to i. m. HAL (r = 0.8205, N = 15, p < 0.001) and not to the PRL responses to i. v. CMI (r = 0.1713, n. s.). It is suggested that the rises in PRL during ECT reflect the responsivity of the hypothalamus-pituitary dopaminergic system, and seem to be the result of a transient decrease in the inhibitory dopaminergic input of the hypothalamus to the pituitary lactotrophs, caused by the electrical stimulus and the subsequent seizure.

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Influence of the dosing interval on prolactin release after remoxipride.

Cited by 9 publications

References 38 publications

The Differential Effects of Atypical Antipsychotics on Prolactin Elevation Are Explained by Their Differential Blood-Brain Disposition: A Pharmacological Analysis in Rats

The Differential Effects of Atypical Antipsychotics on Prolactin Elevation Are Explained by Their Differential Blood-Brain Disposition: A Pharmacological Analysis in Rats

The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

Relationship between prolactin responses to ECT and dopaminergic and serotonergic responsivity in depressed patients

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