PubMed HealthSearch

Biomedical subjects

S Y Yeh

Publications and source records attributed to S Y Yeh.

At least 19 recordsLinked to original sources

Metabolic profile of tripelennamine in humans.

Volunteers were injected im with 100 mg of tripelennamine (pyribenzamine).HCl dissolved in saline. Timed urine was collected. Tripelennamine and its metabolites were identified by GC/MS. Amounts of free tripelennamine excreted in the 0-2-, 2-4-, 4-8-, 8-12-, and 12-24-h urine samples were found to be 0.30, 0.56, 0.17, 0.21, and 0.0%, respectively, of the administered dose. In the same time periods, total tripelennamine (free plus conjugated) amounts were found to be 0.92, 1.20, 0.96, 1.30, and 1.31%, respectively, and total amounts 2-[alpha-hydroxybenzyl(2-dimethylaminoethyl)amino]pyridine(alpha- hydroxytripelennamine) plus an unidentified metabolite were found to be 0.16, 3.35, 3.06, 7.46, and 8.85% of the dose, respectively.

Chromatography, Thin Layer

Cocaine-induced locomotor activity in rats.

Rats were injected SC or IP with a dose of cocaine at 20 mg/kg twice daily or saline (2 ml/kg) for 15 consecutive doses. Horizontal (including ambulatory and repetitive activity) and ambulatory locomotor activities were assessed following the first (acute) and the 15th (chronic) injections. Total locomotor activity (area under curve, AUC) following the acute and the chronic administration of cocaine were comparable, regardless of the route of drug administration. However, the temporal patterns of activity were significantly different; the peak of locomotor activity occurred earlier (chronic vs. acute, 20 vs. 40 min after IP; 130 vs. 180 min after SC) following chronic cocaine administration. Furthermore, the peak activity was significantly higher (3-fold after IP and 50% after SC) in chronically than in acutely treated rats, providing evidence for sensitization. In contrast, activity in the late session (240-280 min after SC) was significantly lower following the chronic SC cocaine administration, providing evidence for desensitization. The absolute slope values of the ascending phase and the descending phase were significantly larger following chronic administration of cocaine than that following the acute dosing. The possibility of changes in locomotor activity with alteration of pharmacokinetics on chronic cocaine treatment is discussed.

Animals

The neurochemical and stimulatory effects of putative metabolites of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine in rats.

Rats were injected SC with a dose of 10 mg/kg (as base) of 3,4-methylenedioxyamphetamine (MDA), or 3,4-methylenedioxymethamphetamine (MDMA), 4-hydroxy-3-methoxyamphetamine, alpha-methyldopamine and alpha-methylnorepinephrine, metabolites of MDA, and alpha-methylepinephrine, a putative metabolite of MDMA, twice daily for either 5 or 7 consecutive doses. The rats were killed 24 h after the last injection and monoamines in discrete brain regions were assayed. MDA, MDMA, 4-hydroxy-3-methoxyamphetamine and alpha-methyldopamine, but not alpha-methylepinephrine, decreased the concentration of serotonin (5-HT) in the frontal cortex. MDA and MDMA, but not 4-hydroxy-3-methoxyamphetamine, alpha-methyldopamine and alpha-methylepinephrine, also decreased the concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortexes. In stimulatory studies, MDA and MDMA, but not their metabolites except alpha-methylepinephrine, which increased activity at 15 and 30 min, increased locomotor activity from 15 to 180 min following the drug administration.

3,4-Methylenedioxyamphetamine

Lack of neurochemical evidence for neurotoxic effects of repeated cocaine administration in rats on brain monoamine neurons.

Rats were injected with cocaine (20 mg/kg, s.c. or i.p. twice daily for 8 days) or saline and killed at 1, 8, 15 or 48 days after the last injection. The concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites, assayed by HPLC-EC, in frontal cortex, hippocampus, striatum, hypothalamus, midbrain, pons-medulla and spinal cord were not significantly different from those in the saline-injected controls at any of the time points examined. These data suggest that the repeated cocaine administration in rats does not produce any long-term depletion in brain catecholamine and 5-HT content suggesting no neurotoxic effects of the drug.

3,4-Dihydroxyphenylacetic Acid

MDMA-induced neurotoxicity: parameters of degeneration and recovery of brain serotonin neurons.

This study investigates a number of parameters that influence the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT) neurons in brain. Both the dose and number of injections of MDMA affect the degree of neurotoxicity on 5-HT axons and terminals as assessed by decreases in the content of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and the density of 5-HT uptake sites. Repeated systemic administration of various doses of MDMA (5-20 mg/kg twice daily for 4 consecutive days) results in dose-dependent decreases in 5-HT, 5-HIAA and 5-HT uptake sites. Increasing the number of injections of MDMA resulted in progressively greater reductions in 5-HT and 5-HIAA which occurred prior to decreases in 5-HT uptake sites. In contrast, no significant changes were observed in the density of norepinephrine uptake sites following single or repeated injections of 20 mg/kg MDMA. With respect to neuronal regeneration, following an initial 90% loss of 5-HT uptake sites after treatment with MDMA, the recovery of these sites occurred over a protracted period of time; a marked 25% reduction was seen at 6 months and the concentration of 5-HT uptake sites returned to control levels at 12 months following treatment with MDMA. Pretreatment with the selective 5-HT uptake blocker, citalopram, prior to each injection of MDMA prevented the neurotoxic effects of MDMA on the 5-HT parameters described above suggesting that active uptake of MDMA or a MDMA-related substance into brain 5-HT neurons was involved in the neurotoxic actions of the drug. In addition, the neurodegenerative effects of MDMA on 5-HT neurons exhibited some species specificity as comparable decreases in cerebral cortical 5-HT, 5-HIAA and 5-HT uptake sites were observed in rat and guinea pig while no significant changes in any of these serotonergic parameters were seen in mouse brain.

3,4-Methylenedioxyamphetamine

3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites.

This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%) in the density of [3H]paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of [3H]mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.

3,4-Methylenedioxyamphetamine

Amniotic fluid phosphatidylglycerol and real-time ultrasonic cephalometry.

The fetal biparietal diameter (BPD) was measured at the time of real-time ultrasound-directed amniocentesis in 159 cases and a phospholipid profile was obtained from the amniotic fluid. BPD measurements of 9.0, 8.7, and 9.2 cm were then compared with a lecithin/sphingomyelin (L/S) ratio greater than or equal to 2.0 for the ability to predict the presence of phosphatidylglycerol (PG) in the profile. The data from the diabetic and nondiabetic patients were analyzed separately. The results demonstrated that in the presence of a L/S ratio greater than or equal to 2.0 the BPD does not aid in the identification of amniotic fluid samples which contain PG in either the diabetic or nondiabetic groups. The data also confirmed previous findings that the BPD is not a reliable predictor of the L/S ratio. It is concluded that for the detection of PG in amniotic fluid, the use of real-time ultrasonic cephalometry cannot substitute for the performance of the phospholipid profile.

Amniotic Fluid

Isolation and identification of morphine n-oxide alpha- and beta-dihydromorphines, beta- or gamma-isomorphine, and hydroxylated morphine as morphine metabolites in several mammalian species.

New morphine metabolites in the urine of guinea pigs, rats, rabbits, cats, monkeys, and humans were isolated with column chromatography, solvent extraction, and TLC and identified with TLC, GLC, and GLC-mass spectrometry. In addition to the known morphine metabolites, morphine N-oxide was isolated from the urine of guinea pigs, and alpha- and beta-dihydromorphines were isolated or detected in the urine of guinea pigs, rats, and rabbits. Monohydroxymorphine was identified tentatively in the urine of guinea pigs, rats, rabbits, and cats. Dihydroxymorphine was identified tentatively in the urine of guinea pigs, rats, and possibly, rabbits. Finally, beta- or gamma-isomorphine was identified tentatively in the urine of guinea pigs. The newly described morphine metabolites may be involved in some long lasting pharmacological effects of morphine.

Animals

The effect of drugs on fetal heart rate variability.

Baseline FHR variability has been quantitated into the mathematical indices of differential index (short-term variability) and interval index (long-term variability). Normal values have been determined. The effect that drugs used during labor have on FHR baseline variability has been evaluated. A clinically meaningful change in variability has been observed following low-dose administration of Demerol, morphine, Nisentil, Phenergan, and Vistaril. A statistically significant increase in variability has been observed following administration of magnesium sulfate.

Analgesics, Opioid

Metabolism and excretion of normorphine in dogs.

Normorphine metabolism was studied in dogs given 20 mg of normorphine hydrochloride/kg sc. Free and (onjugated normorphine excreted in the urine over 144 hr represented 32 and 32%, respectively, of the administered dose. Eighty percent of the urinary excretion of the drug occurred within 9 hr. One percent of the administered dose was excreted as free normorphine in the feces. The urine was chromatographed on a column. Evaporation of the washing and methanolic effluent yielded a residue, which was purified by crystallization from aqueous methanol. Results of UV and IR studies, elemental analysis, and determination of normorphine and glucuronic acid content established the identity of this metabolite as normorphine 3-glucuronide. Dihydronormorphine and dehydronormorphine were detected with GLC-mass spectrometry as minor metabolites.

Animals

Possible effects of normetabolites on the subjective and reinforcing characteristics of opioids in animals and man.

When an opioid capable of forming active metabolites is administered, the total pharmacology is the result of interactions of the opioid and such metabolites, especially normetabolites. Normetabolites may affect the morphine-like characteristics of certain opioids and thus influence their reinforcement in animals and man. Most opioids, when administered in single doses, are positively reinforcing in addicts. Oral administration, as compared with parenteral, facilitates the formation of normetabolites. When chronically administered, many opioids, including acetylmethadol, meperidine, morphine, codeine, propoxyphene, and levorphanol, show evidence of a longer half-life for their normetabolites. Normetabolites may have aversive characteristics and thus impair positive reinforcement of the parent drug in animals and man. For example, addicts do not like chronic oral morphine or chronic oral codeine. Conversely, methadone, the normetabolites of which are inactive, is well accepted during chronic oral administration. Drugs which inhibit N-demethylation will increase the agonist potency of opioids having inactive normetabolites (e.g., methadone) but will decrease the agonist potency of opioids having more potent normetabolites than the parent (e.g., acetylmethadol). The divergent responses of addicts to single doses of opiates as compared with chronic doses indicate that chronic addiction tests in man are needed befored relative abuse liability can be predicted.

Animals

The suspicious contraction stress test.

From a clinical service using the contraction stress test as an evaluator of fetal well-being, a 37-month review of the significance of the suspicious contraction stress test was performed. There were no antepartum losses in a group of 107 patients whose initial test was suspicious. Following each testing a number of patients delivered spontaneously or were delivered for other reasons. Results in 5 of 67 patients at the second testing changed from a suspicious to a positive test, 36 became negative, and 26 remained suspicious. There were no further conversions to a positive test after the second testing. There is a strong correlation between the loss of fetal heart reactivity and the repeated suspicious contraction stress test. The chief value of the suspicious test is as a marker in the high-risk pregnancy appraisal for consideration of additional fetal and maternal evaluation and possible clinical management alteration.

Female

A study of the relationship between Goodwin's high-risk score and fetal outcome.

Correlation between Goodwin's high-risk score and Apgar score was studied in 266 pregnancies managed with the use of the information from clinical monitoring. The correlation coefficients between Goodwin's score and Apgar scores were -0.3178 for one-minute Apgar scores and -0.2668 for five-minute Apgar scores. Both are significant at the level of p less than 0.001. When the patients were divided into two groups by Goodwin's score, fetuses of the group with the higher score (greater than or equal to 4) were significantly more acidotic than those of the group with the lower score. Therefore, Goodwin's high-risk scoring system is simple and useful in the selection of potential risk patients.

Adult

Identification of diacetylmorphine metabolites in humans.

With the techniques of column chromatography, TLC, and GLC, morphine, 6-acetylmorphine, normorphine, morphine 3-glucuronide, 6-acetylmorphine 3-glucuronide, and normorphine glucuronide were identified as metabolites of diacetylmorphine (heroin) in the urine of humans administered 10 mg iv/70 kg body weight.

Adult

Isolation and identification of morphine 3- and 6-glucuronides, morphine 3,6-diglucuronide, morphine 3-ethereal sulfate, normorphine, and normorphine 6-glucuronide as morphine metabolites in humans.

Morphine metabolites were isolated with column chromatography on a resin and neutral aluminum oxide and TLC from the urine of morphine-dependent subjects maintained on morphine sulfate at a dose of 240 mg/day. These metabolites were characterized as morphine 3-glucuronide, morphine 6-glucuronide, morphine 3,6-diglucuronide, morphine 3-ethereal sulfate, normorphine, normorphine 6-glucuronide, and, possibly, normorphine 3-glucuronide by free phenol and glucuronide tests, enzymatic hydrolysis, GLC, TLC, UV spectroscopy, and GLC--mass spectrometry.

Adult

Intrapartum fetal cardiac arrest. A preliminary observation.

In 13 patients, episodes of transient fetal cardiac arrest were observed in a group of 594 extensively monitored labors during a given 3-year period. The number of episodes per patient ranged from one to six, with a maximal duration of cardiac arrest (R-R interval) being 5.2 seconds. All of the patients responded to changing maternal position or termination of pregnancy except 1. This patient received Atropine as a premedication for cesarean section. The parasympatholytic properties of Atropine minimized the severity of cardiac arrest. The effect of cardiac arrest on fetuses is not clearly shown in these preliminary observations. The prompt elimination of cardiac arrest is thought to be imperative in reducing perinatal loss. Cardiac arrest is though to be an extensive form of severe variable deceleration. The hypothesis is made that these fetuses had an unbalanced autonomic nervous system and/or an overwhelming vagal tone. If these signs are detected early by fetal monitoring, attention should be paid to the possibility of cardiac arrest.

Acid-Base Equilibrium

Quantitation of uterine activity in 100 primiparous patients.

An on-line technique for quantitating uterine activity by measuring the total area under the intrauterine pressure curve was utilized during the labor of 100 primiparous patients. Uterine activity was measured in uterine activity units (1 UAU=1 Torr minute). UAU's were calculated for each patient in both cumulative and noncumulative fashions. The rate of uterine activity (UAU per unit of time) increased as labor progressed, yet the total UAU's expended at each centimeter of dilatation progressively decreased with advancing dilatation. Thus, the rate of cervical dilatation increased faster than could be accounted for by the increase in uterine activity. The implication being that the efficiency of uterine contractions increases with advancing labor. It no longer appears reasonable to refer to labor in terms of elapsed time. Information regarding the "pattern of cervical dilatation" and uterine activity appears to be much more meaningful to the evaluation of progress in labor. Quantitation of uterine activity may provide useful information for the ongoing management of labor. Quantitation of UA does provide a means of evaluating the effects of specific events such as medication, anesthesia, and manipulation on UA.

Adolescent