Clinical pharmacology of prochlorperazine in healthy young males.

Isah, AO; Rawlins, MD; Bateman, DN

doi:10.1111/j.1365-2125.1991.tb03973.x

Cited by 41 publications

References 25 publications

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Therapeutic Agents for the Treatment of Migraine

Dubowchik¹,

Macor²

2010

Burger's Medicinal Chemistry and Drug Discovery

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Migraine is a debilitating condition, often with nearly unbearable throbbing pain, nausea, and greatly reduced thresholds to sensory stimulation. Despite the availability of specific acute medications (such as triptans), for over 15 years, migraine remains an undertreated condition. Although representing a revolution in headache therapy at the time, triptans have a number of shortcomings including cardiovascular side effects resulting from their inherent vasoconstrictive properties, and a significant proportion of refractory patients. CGRP antagonists appear to represent the next revolution in migraine therapy, with clinical safety issues shown to be comparable to placebo and 2 h response rates identical to the triptans. Preventative migraine therapy has been dominated by older drugs developed for other indications such as hypertension, epilepsy, and depression. These agents often have significant side effects. Drugs that act on other relevant mechanisms such as ion channels and nitric oxide generation have been developed and tested in the clinic. These have yet to emerge as rivals to the triptans. However, the pathophysiology of migraine is complex and combination therapies that target multiple mechanisms, including one or more of these, may turn out to be more efficacious than monotherapy. An important aspect of migraine therapy that has been addressed with only partial success is speed of onset. Intranasal and pulmonary delivery offer the potential for more rapid systemic exposure and perhaps faster onset of efficacy. Migraine patients are in particular need of improved nonoral drug delivery systems that can provide rapid relief of headache pain along with associated symptoms.

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Therapeutic Agents for the Treatment of Migraine

Dubowchik¹,

Macor²

2010

Burger's Medicinal Chemistry and Drug Discovery

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Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry

Tashiro

Naito

Kagawa

et al. 2011

Biomedical Chromatography

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Oral prochlorperazine (PCZ), an antiemetic, undergoes extensive first-pass metabolism. The study developed a simultaneous analytical method for PCZ and its major metabolites, prochlorperazine sulfoxide (PCZSO), N-demethylprochlorperazine (NDPCZ) and 7-hydroxyprochlorperazine (PCZOH), in human plasma using an isocratic liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Deproteinized plasma specimens were separated using a 3 µm particle size octadecylsilyl column, and the run time was 10 min. The calibration curves were linear over the concentration ranges of 0.01-40 µg/L for PCZ, NDPCZ and PCZOH, and 0.05-80 µg/L for PCZSO. The intra- and inter-assay precisions and accuracies were within 7.0 and 99-104% and within 9.0 and 99-105%, respectively. The lower limits of quantification in human plasma were 10 ng/L for PCZ, NDPCZ and PCZOH, and 50 ng/L for PCZSO. The validated method was applied to the determination of plasma samples in 37 cancer patients receiving PCZ. Large interindividual variations were observed in plasma concentrations of PCZ, PCZSO, NDPCZ and PCZOH (relative standard deviation, 89.4, 88.7, 86.4 and 78.2%, respectively). In conclusion, this simultaneous LC-MS/MS method with acceptable analytical performance can be helpful for evaluating the pharmacokinetics of PCZ, including the determination of its metabolites in cancer patients and in clinical research.

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Psychotropics and Male Reproduction

Drobnis

Nangia

2017

Advances in Experimental Medicine and Biology

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Psychotropic drugs, including antidepressants, antipsychotics, and anticonvulsants, all have negative effects on sexual function and semen quality. These adverse events vary among men and are less pronounced for some medications, allowing their effects to be managed to some extent. Use of specific serotonin reuptake inhibitors (SSRIs) is prevalent in men of reproductive age; and application to treat premature ejaculation increases the number of young men on SSRI therapy. Oxidative damage to sperm can result from prolonged residence in the male reproductive tract. The increase in ejaculatory latency seen with SSRIs likely underlies some of their negative effects on semen quality, including higher sperm DNA fragmentation, seen in all SSRIs evaluated thus far. These medications increase prolactin (PRL) levels in some men, and this is often credited with inhibitory effects on male reproduction; however, testosterone levels are generally normal, reducing the likelihood of direct HPG axis inhibition by PRL. The tricyclic antidepressants have also been shown to increase PRL levels in some studies but not in others. The exception is the tricyclic antidepressant clomipramine, which profoundly increases PRL levels and may depress semen quality. Other antidepressants modulating synaptic levels of serotonin, norepinephrine, and/or dopamine may have toxicity similar to SSRIs, but most have not been evaluated. In limited studies, norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin agonist/reuptake inhibitors (SARIs) have had minimal effects on PRL levels and on sexual side effects. Antipsychotic medications increase PRL, decrease testosterone, and increase sexual side effects, including ejaculatory dysfunction. The greatest evidence is for chlorpromazine, haloperidol, reserpine, risperidone, and thioridazine, with less effects seen with aripiprazole and clozapine. Remarkably few studies have looked at antipsychotic effects on semen quality, and this is an important knowledge gap in reproductive pharmacology. Lithium increases PRL and LH levels and decreases testosterone although this is informed by few studies. The anticonvulsants, many used for other indications, generally decrease free or bioavailable testosterone with variable effects on the other reproductive hormones. Valproate, carbamazepine, oxcarbazepine, and levetiracetam decrease semen quality; other anticonvulsants have not been investigated for this adverse reaction. Studies are required evaluating endpoints of pregnancy and offspring health for psychotropic medications.

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Clinical pharmacology of prochlorperazine in healthy young males.

Cited by 41 publications

References 25 publications

Therapeutic Agents for the Treatment of Migraine

Therapeutic Agents for the Treatment of Migraine

Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry

Psychotropics and Male Reproduction

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