Developmental pharmacology and therapeutics最新文献

{"title":"Methamphetamine detection from meconium and amniotic fluid in guinea pigs depends on gestational age and metabolism.","authors":"K T Nakamura,&nbsp;E L Ayau,&nbsp;C F Uyehara,&nbsp;C L Eisenhauer,&nbsp;L M Iwamoto,&nbsp;D E Lewis","doi":"10.1159/000457483","DOIUrl":"https://doi.org/10.1159/000457483","url":null,"abstract":"<p><p>Significant adverse perinatal effects of maternal methamphetamine use have been reported, but little is known about factors influencing methamphetamine screening test results during the perinatal period. We tested the hypothesis that gestational age would affect quantitative recovery of methamphetamine in meconium and amniotic fluid. Time-bred guinea pigs received an intraperitoneal (i.p.) injection of 1 mg/kg methamphetamine at either 44 days (0.65 of term, n = 5), 50 days (0.74, n = 8), 56 days (0.82, n = 9) or 63 days (0.93, n = 4) gestation. At 1 or 7 days after i.p. methamphetamine, meconium and amniotic fluid were collected for quantitative methamphetamine assay by gas chromatography-mass spectrometry. Recovery from amniotic fluid and meconium 1 day after injection was influenced by gestational age. Greater values in amniotic fluid and meconium and a higher percentage of positive samples were seen in older fetuses. Collectively at all gestational ages, combined testing of amniotic fluid and meconium yielded detectable methamphetamine or its metabolites in 87% of guinea pigs 1 day after injection. However, methamphetamine was not detectable 1 week after injection in any sample (n = 63) at either 0.74 or 0.82 of term except for one positive amniotic fluid sample. Finally, demethylation of methamphetamine to amphetamine was higher in older fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12516762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enantiomers: implications and complications in developmental pharmacology.","authors":"M Eichelbaum","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The majority of synthetic drugs with chiral centers are administered as racemates. Thus chemically, and to an even greater extent biologically, a racemic drug is not a single compound, but a 50:50 mixture of two enantiomeric drugs. No generalization can be made concerning whether and to what extent the activity, in either qualitative or quantitative terms, differs between enantiomers. It is not unusual for the enantiomers of a drug to have a high degree of enantioselectivity for one action but no enantioselectivity for another action. For instance S-propranolol is at least two orders of magnitude more potent than R-propranolol with regard to beta-adrenoceptor antagonism. However, the two enantiomers are equipotent with regard to their membrane stabilizing effect. It is often overlooked that enantioselectivity in the activity of enantiomers as determined in vitro cannot be extrapolated to the in vivo situation since enantioselective drug disposition can lead to an enantiomer ratio in vivo which differs substantially from that in the dosage form administered. Enantioselectivity in drug disposition seems to be the rule rather than the exception and, depending on whether the active or less active enantiomer is preferentially affected, there may be amplification or attenuation of in vivo as compared to the in vitro drug potency.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12480981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental aspects of the monoamine-degrading enzyme monoamine oxidase.","authors":"M Strolin Benedetti,&nbsp;P Dostert,&nbsp;K F Tipton","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the rat heart, monoamine oxidase (MAO)-B activity was shown to predominate in 2- to 3-week-old animals, whereas MAO-A activity was reported to be very low in newborn rats and to increase considerably with age until it predominates. These results are in contrast with those found in the mouse heart, where an age-dependent increase in MAO-B activity with no changes in 5-hydroxytryptamine deaminating activity was found to occur. There is evidence that the adult values of MAO activity are reached early in development in rat kidney and liver. In the rat lung the adult values of MAO-A activity are reached by day 40, whereas MAO-B activity is still increasing by day 80. Important differences have been reported in the developmental pattern of the two forms of MAO in the rat and mouse brain, with a decrease in the MAO-A/MAO-B ratio during postnatal development. In the human brain, the ontogenetic development of MAO-A and MAO-B appears to parallel that observed in the rodent brain. It is worth noting that most of the available data have to be considered with reservation owing to many methodological problems. Further studies are clearly needed to get reliable information on the ontogenesis of MAO in mammalian tissues.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12480988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of phenobarbital on cerebral blood flow in the newborn piglet.","authors":"E Scalais,&nbsp;K Beharry,&nbsp;A Papageorgiou,&nbsp;M Bureau,&nbsp;J V Aranda","doi":"10.1159/000457457","DOIUrl":"https://doi.org/10.1159/000457457","url":null,"abstract":"<p><p>To determine the neonatal cerebrovascular effect of a therapeutic dose and a high dose of phenobarbital (Pb), the effect of Pb on cerebral blood flow (CBF) and total brain oxygen consumption (CMRO2) was studied in three groups of awake newborn piglets (aged 1-3.5 days). Group I (control n = 9) received normal saline solution, group II (n = 9) received a therapeutic dose of Pb (15 mg/kg i.v.) and group III (n = 9) received a high Pb dose (45 mg/kg i.v.). Four CBF measurements per piglet using radioactive microspheres (141Ce, 85Cr, 95Nb, 46Sc), arterial blood gases, O2 content, hematocrit and plasma glucose were obtained at 0, 15, 30, 60 min after saline or Pb injections. In all groups, pH, PaO2, PaCO2, blood pressure, heart rate, temperature and plasma glucose remained unchanged except a 14% decrease (p < 0.01) in blood pressure and an increase (p < 0.05) in PaCO2, 60 min after drug injection in groups II and III. Total CBF in group II decreased by 14% (p < 0.05) 15 min after drug injection and was significantly lower (p < 0.05) than control (group I) but returned to baseline after 30 min. High Pb dose progressively lowered CBF by 11% 15 min after drug injection and produced a significant decrease by 20% (p < 0.01) 30 min after drug injection with return to baseline after 60 min. Similar effects were noted in different brain regions (cerebrum and thalamus). CMRO2 remained unchanged in the control group; however, it was decreased by 35% (< 0.01 p > 0.05) 15 min after drug injection and returned to baseline after 60 min. In group III, high Pb dose lowered CMRO2 by 31% 30 min (p = 0.02) after drug injection. Data indicate that Pb exerts a minimal but transient dose-dependent effect on CBF and CMRO2.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12481060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental transfer of phenobarbital: what is new?","authors":"M P De Carolis,&nbsp;C Romagnoli,&nbsp;S Frezza,&nbsp;E D'Urzo,&nbsp;U Muzii,&nbsp;A Mezza,&nbsp;S Ferrazzani,&nbsp;S De Carolis","doi":"10.1159/000457458","DOIUrl":"https://doi.org/10.1159/000457458","url":null,"abstract":"<p><p>The placental transfer of phenobarbital was investigated in 35 mother-infant pairs at birth. The drug was administered prenatally to the mothers for maternal epilepsy (group 1, n = 5), gestational hypertension and preeclampsia (group 2, n = 20) and prophylaxis of intraventricular hemorrhage in premature deliveries (group 3, n = 10). The phenobarbital levels in arterial cord blood were 100 +/- 2.8% in group 1, 89 +/- 21% in group 2 and 77 +/- 16% in group 3 with respect to the levels observed in the mothers. The most important factor influencing the transplacental passage was the duration of maternal treatment in the infant of group 1 (r = 0.80, p < 0.01), the gestational age in the infants of group 2 (r = 0.74, p < 0.01) and the arterial cord pH in the infants of group 3 (r = 0.89, p < 0.001).</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12481061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed thromboxane synthesis inhibition, but not cholinergic blockade, reverses group B streptococcus-induced pulmonary hypertension.","authors":"J X Li,&nbsp;B M Gray,&nbsp;J R Oliver,&nbsp;C Y Lu,&nbsp;J B Philips","doi":"10.1159/000457461","DOIUrl":"https://doi.org/10.1159/000457461","url":null,"abstract":"<p><p>Anisodamine, an anticholinergic drug, is widely used in China for treatment of infants with septic shock and has been reported to inhibit thromboxane synthesis in cultured cells. Thromboxane A2 plays an important role in the early pulmonary hypertension in sepsis; however, the role of thromboxane A2 later in sepsis is unclear. We tested the hypothesis that thromboxane A2 synthesis inhibition with dazmegrel, and cholinergic blockade with anisodamine, would attenuate the later phase of pulmonary hypertension induced by 4 h of group B streptococcus (GBS) infusion. 1 mg/kg of dazmegrel reversed the pulmonary hypertension and slightly increased cardiac output; these hemodynamic improvements persisted for 30-60 min. Plasma thromboxane B2 levels returned toward pre-GBS baseline values after dazmegrel treatment. Thus, thromboxane A2 is still a major mediator of pulmonary hypertension in piglets after 4 h of continuous GBS infusion. 0.5 mg/kg of anisodamine had no significant hemodynamic effect. 2 and 4 mg/kg of anisodamine each caused transient, dose-related decreases in systemic artery pressure; cardiac output also fell after the highest anisodamine dose. Pulmonary hypertension was not alleviated by anisodamine. All hemodynamic changes induced by anisodamine were short-lived and returned to preanisodamine values within 10 min. Anisodamine did not ameliorate thromboxane-mediated pulmonary hypertension in this animal model, and therefore may not inhibit thromboxane synthesis in vivo. The results of this study do not support the use of anticholinergic therapy to improve hemodynamics in GBS sepsis, but do suggest that thromboxane synthesis inhibition may be a clinically useful therapy in advanced GBS sepsis.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12481064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulation of renal tubular transport of p-aminohippurate in rats of different ages by treatment with adrenocortical steroids.","authors":"H Bräunlich,&nbsp;H Rassbach,&nbsp;S Vogelsang","doi":"10.1159/000457455","DOIUrl":"https://doi.org/10.1159/000457455","url":null,"abstract":"<p><p>Treatment with prednisolone or dexamethasone is followed by an increase in renal excretion of p-aminohippurate (PAH) and in accumulation of PAH in renal cortical slices, particularly in 5- and 10-day-old rats with immature kidney function. Treatment with triamcinolone is effective both in immature and in 55-day-old rats. There is no stimulation of PAH transport after treatment with mineralocorticoids (desoxycorticosterone, aldosterone).</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000457455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12481127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional changes implicating dopaminergic systems following perinatal treatments.","authors":"T Archer,&nbsp;A Fredriksson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A series of experiments, involving diverse perinatal treatments of either rats or mice, have been performed in order to investigate the effects of these treatments upon certain selected spontaneous and learned behaviors in the laboratory. Rat dams were administered either metallic mercury, organic tin or neuroleptic compounds, and the offspring of these dams was studied with behavioral tests at adult ages, prenatal studies. Newborn rat pups were administered either 6-hydroxydopamine (6-OHDA) (at various doses), or metallic mercury and then tested at adult ages. Newborn mice were administered either metaclopramide, an antiemetic compound, or haloperidol, a neuroleptic compound, and tested for spontaneous and d-amphetamine induced activity as adults. The behavioral battery the rats were tested with consisted of measures of spontaneous motor activity, including locomotion/ambulation, rearing, and head dipping behaviors, and a parameter under which diverse behaviors were collected, total activity. Alterations to instrumental maze learning performance were studied through application of the spatial learning tasks: the radial arm maze and the circular swim maze. Possible changes in dopaminergic pathways were assessed by measuring the effects of perinatal treatments upon d-amphetamine-induced activity. It was shown that prenatal metallic mercury, organic tin and the neuroleptic compounds, haloperidol and remoxipride altered various parameters of spontaneous motor activity, retarded maze learning in the radial arm maze and potentiated d-amphetamine-induced activity. Metallic mercury rats were not subjected to the amphetamine test and remoxipride rats were not retarded according to the learning task. Postnatal metallic mercury, 6-OHDA, haloperidol and the antiemetic compound, metaclopramide, also altered spontaneous and d-amphetamine-induced activity as well as radial arm maze performance, excluding in this case haloperidol and metaclopramide. None of these treatments altered performance in the circular swim maze, except for 6-OHDA where doses inflicting severe depletions (greater than 85% depletion compared to control values) caused notable impairments. One tentative conclusion from the pattern of behavioral changes, generally in the absence of any measurable neurochemical changes, observed after these treatments is that the functional development of dopaminergic systems had, to a greater or lesser degree, been altered.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12481597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of nimodipine on brain blood flow following acute brain ischemia in the newborn piglet.","authors":"C. Easley, F. Wartman, A. Kopelman, T. Louis","doi":"10.1159/000480599","DOIUrl":"https://doi.org/10.1159/000480599","url":null,"abstract":"We examined the effect of the calcium channel blocker nimodipine on postischemic hypoperfusion in the newborn piglet brain. A severe pneumothorax (SP) was induced by injecting air into the right thorax until the mean arterial blood pressure fell to 25% of baseline and was maintained for 4 min. Blood flow was immediately reduced 70-90% from baseline in each brain region during SP. In untreated animals postischemic hypoperfusion existed at 60 min, following recovery from SP with regional brain blood flow reduced 20-30% from baseline. Nimodipine infusion after SP prevented postischemic hypoperfusion in all brain regions and increased blood flows by as much as 40% above baseline in midbrain and brainstem structures. Nimodipine infusion began after severe brain ischemia prevented postischemic hypoperfusion and enhanced brain blood flow in this model.","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86512738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxic-ischemic damage in the neonatal brain: excitatory amino acids.","authors":"H Hagberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Perinatal brain damage is a major clinical problem. Recent studies suggest that excitatory amino acids (EAAs) may be important for the development of hypoxic-ischemic brain injury in the newborn. Experimental work demonstrates that the immature brain is hypersensitive to the toxic effects EAA ('excitotoxicity'), hypoxic-ischemia is accompanied by an extracellular overflow of EAAs and hypoxic-ischemic brain damage is reduced by EAA receptor antagonists. Clinical investigations demonstrate the presence of EAA receptors in vulnerable areas of the newborn human brain and the concentrations of EAAs in the cerebrospinal fluid are higher in asphyxiated than in control infants. Clinical studies are warranted to evaluate the importance of excitotoxicity for development of brain lesions after severe asphyxia.</p>","PeriodicalId":11160,"journal":{"name":"Developmental pharmacology and therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12480983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}