Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EPHEDRINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1986

NTP Toxicology and Carcinogenesis Studies of Ephedrine Sulfate (CAS No. 134-72-5) in F344/N Rats and B6C3F1 Mice (Feed Studies).

Ephedrine sulfate is a sympathomimetic amine that affects both the central and peripheral nervous systems. An effective bronchiodilator and weak vasoconstrictor, ephedrine sulfate is used extensively in nonprescription pharmaceutical preparations such as nose drops, cold tablets, cough syrups, and, in particular, asthma relief medicines. Ephedrine sulfate was nominated for carcinogenesis studies by the National Cancer Institute because of its widespread and long-term use for the relief of symptoms associated with asthma. In 14-day repeated-exposure studies, F344/N rats of each sex received diets containing 0-1,500 ppm ephedrine sulfate or drinking water containing 0-1,200 ephedrine sulfate; B6C3F1 mice received diets or drinking water containing 0-5,000 ppm ephedrine sulfate. In the feed studies, the average feed consumption by dosed rats and mice was comparable to that of their respective controls. The average water consumption by rats and mice decreased with increasing concentration of ephedrine sulfate in the drinking water. Thus, subsequent studies used the feed route of administration. Doses for the 2-year studies were selected on the basis of results from 13-week studies in which F344/N rats of each sex were given diets containing 0, 125, 250, 500, 1,000, or 2,000 ppm ephedrine sulfate and B6C3F1 mice of each sex were given diets containing 0, 310, 630, 1,250, 2,500, or 5,000 ppm ephedrine sulfate. The major response that occurred during the 13-week studies was compound-associated reduction in weight gain. Toxicology and carcinogenesis studies of ephedrine sulfate were conducted by administering diets containing 0, 125, or 250 ppm ephedrine sulfate to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. The estimated average amount of ephedrine sulfate consumed per day during the 2-year study was 4 mg/kg and 9 mg/kg for low dose and high dose male rats, 5 mg/kg and 11 mg/kg for female rats, 14 mg/kg and 29 mg/kg for male mice, and 12 mg/kg and 25 mg/kg for female mice. Survival of chemically exposed female rats during the 2-year study was greater than that of the controls (control, 27/50; low dose, 39/50; high dose, 39/50); survival of exposed male rats and male and female mice was comparable to that of controls. Throughout most of the 2-year studies, mean body weights of rats and mice of each sex receiving diets containing ephedrine sulfate were lower than those of controls. Neoplasms that occurred in these studies were not considered to be related to administration of ephedrine sulfate. Two high dose female mice had ovarian granulosa cell tumors, and luteomas were found in one low dose and one high dose female mouse. Because of the low incidence, these uncommon, benign tumors could not be clearly related to ephedrine sulfate administration. Ephedrine sulfate was not mutagenic in four strains of Salmonella typhimurium (TA100, TA1535, TA97, or TA98) with or without Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver S9 activation. Ephedrine sulfate did not induce sister-chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells. An audit of the experimental data was conducted for these 2-year studies of ephedrine sulfate. No data discrepancies were found that influenced the final interpretations. Under the conditions of these studies, there was no evidence of carcinogenicity for F344/N rats or B6C3F1 mice of either sex receiving 125 or 250 ppm ephedrine sulfate in the diet for 2 years.

Journal Article↗
PubMed1998

Discriminative stimulus properties of (-)ephedrine.

Ephedrine, a structural analog of methamphetamine, is one of the major constituents of legally available herbal dietary supplements. Although racemic ephedrine and ephedra extract have been previously used as training drugs in drug discrimination studies, there is evidence that the two optical isomers of ephedrine do not produce identical amphetamine-like stimulus effects in rats. Consequently, we trained a group of six male Sprague-Dawley rats to discriminate 4 mg/kg of the more potent optical isomer of ephedrine, (-)ephedrine, from saline vehicle. The (-)ephedrine stimulus (ED50 = 0.8 mg/kg) generalized to other central stimulants such as S(+)amphetamine (ED50 = 0.4 mg/kg), cocaine (ED50 = 2.7 mg/kg), methylphenidate (ED50 = 1.2 mg/kg), S(-)methcathinone (ED50 = 0.3 mg/kg), and caffeine (ED50 = 36.7 mg/kg), but stimulus generalization failed to occur to either S(+)methamphetamine or N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA). In addition, although we have previously shown that a (+)amphetamine stimulus generalizes to (-)ephedrine but not to (+)ephedrine, in the present investigation the (-)ephedrine stimulus generalized to (+)ephedrine (ED50 = 2.6 mg/kg). From the findings (a) that (-)ephedrine is approximately 10 times less potent than (+)amphetamine in (+)amphetamine-trained rats, whereas it is only half as potent as (+)amphetamine in (-)ephedrine-trained animals; (b) that the (-)ephedrine stimulus failed to generalize to (+)methamphetamine; and (c) that the (-)ephedrine stimulus generalized to (+)ephedrine, it is concluded that the stimulus effects of (+)amphetamine and (-)ephedrine as training drugs, while similar, are not identical. It is also concluded that the stimulus effects of (-)ephedrine and those of the designer drug MDMA, while perhaps sharing some amphetaminergic commonality, are nonidentical.

Animals↗
PubMed2005

Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects.

AIM: The combination of ephedrine and caffeine has been used in herbal products for weight loss and athletic performance-enhancement, but the pharmacokinetic profiles of these compounds have not been well characterized. This study aimed to develop a mechanistic model describing ephedrine, norephedrine, and caffeine pharmacokinetics and their interactions in healthy subjects. METHODS: The pharmacokinetic model was developed based on the simultaneous modelling using plasma samples gathered from two clinical trials. The treatments consisted of single-doses of pharmaceutical caffeine and ephedrine, given alone or together, and an herbal formulation containing both caffeine and ephedrine. We used a mixed-effect statistical model and the program NONMEM to take account of intersubject variability. RESULTS: Three hundred and seventy-nine ephedrine, 352 norephedrine, 417 caffeine plasma concentrations and 40 ephedrine urine concentrations were obtained from 24 subjects. A one-compartment model with first-order absorption described the caffeine data. Caffeine clearance was 0.083 l min(-1) (CV 38%) and decreased to 0.038 l min(-1) in presence of oral contraceptive therapy, its volume of distribution was 38.6 l (CV 20%) and its absorption rate constant was 0.064 l min(-1) (CV 50%). A four-compartment model described the pharmocokinetics of ephedrine and norephedrine. Ephedrine was eliminated mostly renally, with a clearance of 0.34 l min(-1) (CV 11%), and a volume of distribution of 181 l (CV 19%). Nonlinearity in the conversion of ephedrine to norephedrine was observed. Different models showed that the simultaneous administration of caffeine, or the amount of caffeine in the absorption compartment, was associated with a slower rate of absorption of ephedrine. A 32% greater relative bioavailability of herbal compared with pharmaceutical ephedrine administration was observed. CONCLUSIONS: We describe a mechanistic model for ephedrine, norephedrine and caffeine pharmacokinetics and their interactions. The relative bioavailability of ephedrine differed between the herbal supplement compared with the pharmaceutical formulation. Concomitant ingestion of caffeine slowed the absorption rate of ephedrine, which is mainly related to the amount of the former in the absorption compartment. A saturable process appears to be involved in the metabolism of ephedrine to norephedrine.

Administration, Oral↗
PubMed1999

Direct effects of ephedrine isomers on human beta-adrenergic receptor subtypes.

Ephedrine and its alkaloids are used for the treatment of asthma, nasal congestion, and obesity. Ephedrine, with two chiral centers, exists as four isomers that exhibit direct and indirect effects on both alpha- and beta-adrenergic receptors (AR). Our main goal was to study the direct effects of the ephedrine isomers on human beta1-, beta2-, and beta3-AR expressed in Chinese hamster ovary cells. Previous work indicated that the ephedrine isomers are inactive as agonists and that 1R,2S-ephedrine is more potent than the 1S,2R-isomer as an antagonist of catecholamine-induced lipolysis in rat adipose tissue (Lee et al., J Pharmacol Exp Ther 190: 249-259, 1974). Stimulation of adenylyl cyclase, associated with cyclic AMP accumulations, was measured by a luciferase reporter gene assay. On human beta1-AR, the rank order of potency (EC50 values, maximal response relative to isoproterenol = 100%) was 1R,2S-ephedrine (0.5 microM, 68%) > 1S,2R-ephedrine (72 microM, 66%) > 1S,2S-pseudoephedrine (309 microM, 53%) = 1R,2R-pseudoephedrine (1122 microM, 53%). On human beta2-AR, the rank order of potency was 1R,2S-ephedrine (0.36 microM, 78%) > 1R,2R-pseudoephedrine (7 microM, 50%) > or = 1S,2S-pseudoephedrine (10 microM, 47%) > 1S,2R-ephedrine (106 microM, 22%). Only 1R,2S-ephedrine showed significant agonist activity on human beta3-AR with an EC50 = 45 betaM and a maximal response of 31%. Our studies demonstrated that (a) stereoselective and rank order differences exist among the direct effects of ephedrine isomers; (b) 1R,2S-ephedrine is the most potent of the four ephedrine isomers on all three human beta-AR; and (c) 1R,2S- ephedrine was nearly equipotent as a beta1-/beta2-AR agonist and the only isomer possessing weak partial agonist activity on beta3-AR.

Adrenergic beta-Agonists↗
PubMed1999

Acute effect of ephedrine on 24-h energy balance.

Ephedrine is used to help achieve weight control. Data on its true efficacy and mechanisms in altering energy balance in human subjects are limited. We aimed to determine the acute effect of ephedrine on 24-h energy expenditure, mechanical work and urinary catecholamines in a double-blind, randomized, placebo-controlled, two-period crossover study. Ten healthy volunteers were given ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately measures minute-by-minute energy expenditure and mechanical work. Measurements were taken of 24-h energy expenditure, mechanical work, urinary catecholamines and binding of (+/-)ephedrine in vitro to human beta1-, beta2- and beta3-adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965+/-1301 versus 8648+/-1347 kJ, P<0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032+/-0.011 microg/mg creatinine) compared with placebo (0.044+/-0.012 microg/mg creatinine) (P<0.05). (+/-)Ephedrine is a relatively weak partial agonist of human beta1- and beta2-adrenoreceptors, and had no detectable activity at human beta3-adrenoreceptors. Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal human subjects. A lack of binding of ephedrine to beta3-adrenoreceptors and the observed decrease in urinary noradrenaline during ephedrine treatment suggest that the thermogenic effect of ephedrine results from direct beta1-/beta2-adrenoreceptor agonism. An indirect beta3-adrenergic effect through the release of noradrenaline seems unlikely as urinary noradrenaline decreased significantly with ephedrine.

Adrenergic alpha-Agonists↗
PubMed2001

Phenylephrine added to prophylactic ephedrine infusion during spinal anesthesia for elective cesarean section.

BACKGROUND: Because ephedrine infusion (2 mg/min) does not adequately prevent spinal hypotension during cesarean delivery, the authors investigated whether adding phenylephrine would improve its efficacy. METHODS: Thirty-nine parturients with American Society of Anesthesiologists physical status I-II who were scheduled for cesarean delivery received a crystalloid preload of 15 ml/kg. Spinal anesthesia was performed using 11 mg hyperbaric bupivacaine, 2.5 microg sufentanil, and 0.1 mg morphine. Maternal heart rate and systolic blood pressure were measured at frequent intervals. A vasopressor infusion was started immediately after spinal injection of either 2 mg/min ephedrine plus 10 microg/min phenylephrine or 2 mg/min ephedrine alone. Treatments were assigned randomly in a double-blind fashion. The infusion rate was adjusted according to systolic blood pressure using a predefined algorithm. Hypotension, defined as systolic blood pressure less than 100 mmHg and less than 80% of baseline, was treated with 6 mg ephedrine bolus doses. RESULTS: Hypotension occurred less frequently in the ephedrine-phenylephrine group than in the ephedrine-alone group: 37% versus 75% (P = 0.02). Ephedrine (36+/-16 mg, mean +/- SD) plus 178+/-81 microg phenylephrine was infused in former group, whereas 54+/-18 mg ephedrine was infused in the latter. Median supplemental ephedrine requirements and nausea scores (0-3) were less in the ephedrine-phenylephrine group (0 vs. 12 mg, P = 0.02; and 0 vs. 1.5, P = 0.01, respectively). Umbilical artery pH values were significantly higher in the ephedrine-phenylephrine group than in the group that received ephedrine alone (7.24 vs. 7.19). Apgar scores were similarly good in both groups. CONCLUSION: Phenylephrine added to an infusion of ephedrine halved the incidence of hypotension and increased umbilical cord pH.

Adult↗
PubMed2003

Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis.

CONTEXT: Ephedra and ephedrine sometimes are used for weight loss or enhanced athletic performance, but the efficacy and safety of these compounds are uncertain. OBJECTIVE: To assess the efficacy and safety of ephedra and ephedrine used for weight loss and enhanced athletic performance. DATA SOURCES: We searched 9 databases using the terms ephedra, ephedrine, adverse effect, side effect, efficacy, effective, and toxic. We included unpublished trials and non-English-language documents. Adverse events reported to the US Food and Drug Administration MedWatch program were assessed. STUDY SELECTION: Eligible studies were controlled trials of ephedra or ephedrine used for weight loss or athletic performance and case reports of adverse events associated with such use. Eligible studies for weight loss were human studies with at least 8 weeks of follow-up; and for athletic performance, those having no minimum follow-up. Eligible case reports documented that ephedra or ephedrine was consumed within 24 hours prior to an adverse event or that ephedrine or an associated product was found in blood or urine, and that other potential causes had been excluded. Of the 530 articles screened, 52 controlled trials and 65 case reports were included in the adverse events analysis. Of more than 18 000 other case reports screened, 284 underwent detailed review. DATA EXTRACTION: Two reviewers independently identified trials of efficacy and safety of ephedra and ephedrine on weight loss or athletic performance; disagreements were resolved by consensus. Case reports were reviewed with explicit and implicit methods. DATA SYNTHESIS: No weight loss trials assessed duration of treatment greater than 6 months. Pooled results for trials comparing placebo with ephedrine (n = 5), ephedrine and caffeine (n = 12), ephedra (n = 1), and ephedra and herbs containing caffeine (n = 4) yielded estimates of weight loss (more than placebo) of 0.6 (95% confidence interval, 0.2-1.0), 1.0 (0.7-1.3), 0.8 (0.4-1.2), and 1.0 (0.6-1.3) kg/mo, respectively. Sensitivity analyses did not substantially alter the latter 3 results. No trials of ephedra and athletic performance were found; 7 trials of ephedrine were too heterogeneous to synthesize. Safety data from 50 trials yielded estimates of 2.2- to 3.6-fold increases in odds of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations. Data are insufficient to draw conclusions about adverse events occurring at a rate less than 1.0 per thousand. The majority of case reports are insufficiently documented to allow meaningful assessment. CONCLUSIONS: Ephedrine and ephedra promote modest short-term weight loss (approximately 0.9 kg/mo more than placebo) in clinical trials. There are no data regarding long-term weight loss, and evidence to support use of ephedra for athletic performance is insufficient. Use of ephedra or ephedrine and caffeine is associated with increased risk of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations.

Anti-Obesity Agents↗