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PubMedDate not supplied

[Effect of caffeine on tension development of skeletal muscle of mdx mouse].

Among various pharmacological actions of caffeine upon the skeletal muscle, activation of the contractile system by Ca2+ is also influenced by caffeine. So far the effect of caffeine upon the contractile system is not properly studied in pathological muscle specimens. Using the skinned muscle fiber, we compared the effect of caffeine between control and dystrophic (mdx) mouse muscle. In lower Ca2+ (-5 microM), tension generation increased with caffeine. A maximum tension generation in higher Ca2+ (10-30 microM) was suppressed by 30 mM caffeine. In comparison between control and mdx type 2 muscle fiber, tension with caffeine was always more in mdx. On the other hand, modification by 5 mM caffeine was the same between control and mdx type 1 fiber of the soleus muscle. Different responses to caffeine between control and mdx type 2 fiber might be related to prevalent degenerative or regenerative processes. But exact mechanism is not clear yet. Currently, contracture by caffeine or halothane is applied in diagnosis of malignant hyperthermia (MH). Present observations suggested that influence of caffeine on the contractile system constituted one of causes for unspecific results in cases with concurrent neuromuscular diseases.

Animals↗
PubMedDate not supplied

[1H-NMR analysis of heteroassociation of caffeine with antibiotic actinomycin D in the aqueous solution].

The molecular basis of the action of caffeine as a complex forming agent, an interceptor of aromatic drugs intercalating into DNA was studied by the example of the an anticancer antibiotic actinomycin D examined. The hetero-association of caffeine and actionomycin D was studied by one- and two-dimensional 1H-NMR spectroscopy (500 MHz). Concentration and temperature dependences of the proton chemical shifts of molecules in aqueous solution were measured. The equilibrium reaction constant of hetero-association of caffeine with actinomycin D (K = 246 +/- 48 M-1), the limiting chemical shifts of caffeine protons in complexes were determined. The most favourable structure of the 1:1 caffeine-actinomycin D hetero-complex in aqueous solution was constructed using the calculated values of the induced proton chemical shifts of molecules and the quantum-mechanical iso-shielding curves for caffeine and actinomycin D. The thermo-dynamical parameters of the hetero-complex formation between caffeine and actinomycin D were also determined. The structural and thermo-dynamical analysis showed that dispersive forces and hydrophobic interactions play the major role in hetero-association of caffeine and actinomycin D in aqueous-salt solution. The relative content of different complexes in mixed solutions containing caffeine and actinomycin D was calculated and distinctive features of the dynamic equilibrium of caffeine-actinomycin D hetero-associates were revealed as a function of concentration and temperature. It is concluded that hetero-association of caffeine and actinomycin D molecules a lowers the effective concentration of the drug in solution and hence the pharmacological activity of actinomycin D.

Anti-Bacterial Agents↗
PubMed1990

In vitro caffeine induced aortic smooth muscle reactivity in rat.

The effects of caffeine on aortic smooth muscle contractility during hypertension were studied in SHR and WKY control rats. To compare the effects of Mg++ on vascular reactivity induced by caffeine 1.2 mM MgCl2 was either included or omitted from the Krebs solution bathing the aortic tissue. The role of alpha-adrenergic receptors and verapamil-sensitive Ca++ channels in eliciting caffeine induced contraction in aortic tissues was also examined in Sprague Dawley rats. We report that the aortic smooth muscle from SHR animal was less responsive than WKY aortic smooth muscle to 10 and 20 mM concentrations of caffeine. Caffeine induced a relaxation of aortic smooth muscle contracted with 60 mM KCl or 10(-7) M NE. However, the relaxation response was slower in SHR as compared to WKY rats. To assess the involvement of alpha-adrenergic receptors in caffeine induced aortic contractility alpha 1- and alpha 2-receptors were blocked with 10(-7) M prazosin and 10(-7) M yohimbine respectively. The caffeine induced aortic contractility did not seem to involve alpha-adrenergic receptors. A blockade of verapamil sensitive Ca++ channels with 10(-7) M verapamil failed to inhibit caffeine induced aortic contractility. These results indicate that caffeine involves release of Ca++ in vascular muscle, however, Ca++ is released from a site other than the one controlled by alpha-adrenergic receptors. Also, the Ca++ channels involved are other than the Verapamil sensitive Ca++ channels. Yet it is clear that if the aortic contractility is due to Ca++ release alone, then caffeine is a potent agent for Ca++ release in the aortic smooth muscle of rat. Additionally, the caffeine-sensitive mechanism for aortic smooth muscle contraction is impaired during hypertension.

Animals↗
PubMed1989

Mechanism of increased hepatotoxicity of acetaminophen by the simultaneous administration of caffeine in the rat.

The simultaneous administration of caffeine has been shown to potentiate acetaminophen-induced hepatotoxicity. In the present study, the mechanisms of this effect were studied. Male Sprague-Dawley rats, fasted for 18 hr, were given acetaminophen (0.5 g/kg) and/or caffeine (0.1 g/kg) i.p. Two hours later, the depletion of hepatic reduced glutathione (GSH) induced by acetaminophen was more pronounced by the concomitant administration of caffeine, although the effect of caffeine alone on the hepatic GSH content was minimal at this dose. Covalent binding of a reactive metabolite of acetaminophen to hepatic proteins was increased by caffeine although the free acetaminophen content in the liver was not affected. In isolated rat hepatocytes prepared from normal animals, caffeine enhanced acetaminophen-induced GSH depletion and potentiated covalent binding of the reactive metabolite to cellular proteins. The extracellular release of GSH + oxidized glutathione was decreased by acetaminophen, and this decrease was potentiated further by the addition of caffeine. In the cells, the production of acetaminophen-GSH conjugate also was increased in the presence of caffeine, whereas that of glucuronide conjugate was decreased. In microsomes, NADPH-dependent production of acetaminophen-GSH conjugate was increased in the presence of caffeine. Thus, caffeine appears to potentiate acetaminophen-induced hepatotoxicity mainly by enhancing the production of a reactive metabolite of acetaminophen by mixed function oxidases. To what extend caffeine-induced GSH depletion plays a role is to be clarified.

Acetaminophen↗
PubMed1988

Influence of caffeine consumption on carcinomatous and normal mammary gland development in mice.

The influence of caffeine consumption on the development of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in BD2F1 female mice and spontaneous mammary carcinomas in nulliparous C3H mice was examined. Caffeine (250 and 500 mg/liter of drinking water) was administered to BD2F1 mice commencing 1 week after a series of 6 weekly 7,12-dimethylbenz(a)anthracene intubations, until experiment termination. Caffeine was administered to C3H mice (via drinking water) commencing at 8 weeks of age to experiment termination. In BD2F1 mice receiving 250 and 500 mg of caffeine, mammary carcinoma multiplicity (number of mammary carcinomas/mouse) was increased by 20 and 40%, respectively. In C3H mice receiving 250 and 500 mg caffeine, mammary carcinoma multiplicity was increased by 13 and 117%, respectively. In both BD2F1 and C3H mice, the higher dose level of caffeine resulted in a significant (P less than 0.05) increase in mammary carcinoma multiplicity. Caffeine consumption did not significantly effect the percentage of mice bearing mammary carcinomas or the mean latency period of mammary tumor appearance. In a second series of studies, the influence of caffeine consumption on mammary gland development in female BALB/c mice was assessed in vivo and in vitro (organ culture). In mice consuming caffeine (500 mg/liter of drinking water), mammary gland development was significantly (P less than 0.05) increased compared to control mice; this difference in mammae development was more conspicuous in mice treated with mammotropic hormones. In the organ culture studies, mammary glands derived from caffeine (500 mg/liter of drinking water) consuming BALB/c mice were more responsive in vitro to a mammotropic hormonal developmental growth stimulus than were mammae derived from control mice (P less than 0.05). These results provide evidence that caffeine consumption can enhance mammary tumorigenesis in C3H and carcinogen-treated BD2F1 female mice and, in addition, enhance developmental growth of the normal female mouse (BALB/c) mammary gland.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Psychomotor stimulant effects of caffeine alone and in combination with an adenosine analog in the squirrel monkey.

Responding of squirrel monkeys was maintained under a fixed-interval schedule of food presentation in one group of subjects or electric-shock presentation in a second group. Rates of responding were decreased in a dose-dependent manner by the (-)-isomer of 6N-[1-methyl-2-phenylethyl]-adenosine (PIA) under both schedules. Caffeine shifted the (-)-PIA dose-effect curve to the right in a dose-dependent manner. Single administrations of 15.0 mg/kg of caffeine had (-)-PIA-antagonist effects for up to 48 hr. Caffeine administered alone increased rates of responding at intermediate doses, and decreased rates at the highest doses. The increases in response rates produced by intermediate doses of caffeine were appreciably diminished at 24 hr. Doses of (-)-PIA that were inactive when administered alone had little effect on the increases in response rate produced by caffeine. Doses of (-)-PIA that decreased response rates when administered alone attenuated the increase in response rates produced by caffeine. Increases in response rates produced by (+)-amphetamine were altered by (-)-PIA similarly to the manner in which (-)-PIA altered the effects of caffeine. Increases in response rates produced by caffeine were altered by chlorpromazine similarly to the manner in which (-)-PIA altered effects of caffeine. When caffeine was administered daily, as one 15.0-mg/kg injection after experimental sessions, tolerance developed to the response rate increasing effects of caffeine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1986

Elimination of chronically consumed caffeine in the pregnant monkey (Macaca fascicularis).

Characterization of alterations in caffeine elimination during pregnancy is essential in assessing the potential exposure of the fetus to caffeine and its metabolites. Female monkeys (Macaca fascicularis) were exposed to caffeine in their drinking water 7 days/week before, during and after pregnancy. The low exposure (0.15 mg/ml) corresponded to a level sometimes consumed by pregnant women (10-15 mg/kg/day) whereas the high exposure (0.35 mg/ml) was above average human consumption (25-30 mg/kg/day). Blood samples and 24-hr urine samples were collected every 2 weeks throughout dosing. Caffeine and metabolite concentrations in serum and urine were determined by high-performance liquid chromatography. Before pregnancy, geometric mean serum caffeine concentrations were approximately 1.6 and 4.9 micrograms/ml and serum theophylline concentrations were 6.6 and 13.3 micrograms/ml for the low and high dose groups, respectively. During pregnancy, serum caffeine concentrations increased by approximately 100% for both dose groups and, after parturition, declined to prepregnancy concentrations. Serum theophylline concentrations were usually greater than serum caffeine concentrations and did not change during pregnancy. The amount of caffeine and theophylline excreted in the urine over 24 hr increased during pregnancy and returned to prepregnancy levels after parturition. The results of this study indicate that pregnancy decreased caffeine elimination, resulting in a significant increase in serum caffeine levels. The changes in caffeine elimination may be related to alterations in serum estrogen and progesterone levels.

Animals↗
PubMed1987

Delay in caffeine elimination in breast-fed infants.

Because of a persistently elevated caffeine half-life observed in a breast-fed infant during caffeine maintenance therapy, we conducted this prospective longitudinal study in two groups of infants (five exclusively breast-fed and 12 formula-fed). After 46 weeks' postconceptional age, all five breast-fed infants had a marked delay in caffeine elimination, compared with one infant in the formula-fed group. Four breast-fed infants had measurements of significantly longer caffeine half-lives compared with 12 formula-fed infants (76 +/- 13 hours v 21 +/- 28 hours and 54 +/- 9 hours v 16 +/- 13 hours at 47 to 50 weeks and 51 to 54 weeks postconceptional age, respectively), as well as significantly higher trough blood levels (three- to five-fold) after 46 weeks' postconceptional age. The fifth breast-fed infant accumulated caffeine secondary to a steep increase in caffeine half-life from 102 hours at 44 weeks to 372 hours at 51 weeks. The elevated blood caffeine levels in breast-fed infants was not related to higher daily dosage of caffeine citrate (4.4 mg/kg compared with 8.3 mg/kg in the formula-fed group at 56 weeks' postconceptional age). Daily consumption of caffeine was low or nonexistent in four nursing mothers, and transfer of caffeine to the infant was considered to be trivial. The findings from this study suggest, as does breast milk jaundice due to inhibition of glycuronyl transferase, that some components of human milk (free fatty acid, lipase activity, or other factors) inhibit or repress the postnatal normal maturation process of caffeine metabolism by hepatic cytochrome P-450.

Apnea↗
PubMed1984

Disposition of dietary caffeine in milk, saliva, and plasma of lactating women.

Caffeine is present in many dietary substances; its appearance from these sources in human milk has not previously been studied in detail. Fifteen lactating women ingested a known amount of a caffeinated beverage (36 to 335 mg). Simultaneous milk and saliva samples were collected at intervals for the subsequent 12 hours and assayed for caffeine content. Eleven of 15 mothers excreted measurable caffeine in milk. Caffeine was detected by 15 minutes in saliva and milk; peak levels in milk (2.09 to 7.17 micrograms/mL) and saliva (1.24 to 9.22 micrograms/mL) were achieved within 1 hour. Elimination half-lives were 1.3 to 13.5 hours (mean 4.0 +/- 3.7 [SD] hours) for saliva and 1.5 to 14.5 hours (mean 6.1 +/- 4.4 [SD] hours) for milk. Assuming each infant would ingest 90 mL of milk every three hours for 24 hours after maternal ingestion of caffeine, it is possible to estimate potential exposure of the nursing infant to caffeine. The amount of caffeine available for infant absorption ranged from 0.01 to 1.64 mg or 0.06% to 1.5% of the maternal dose. Caffeine was not present in the infants' urine collected for five hours after the first nursing period. The maternal ingestion of a single cup of caffeinated beverage does not appear to present significant doses of caffeine to the nursing infant.

Adult↗
PubMed1983

Inhibition of caffeine elimination by short-term ethanol administration.

Short-term ethanol ingestion has been shown to inhibit the metabolism of a number of drugs metabolized by cytochrome P-450 in both man and laboratory animals. However, the effects of short-term ethanol administration on the metabolism of cytochrome P-448-dependent drugs in man is unknown. Caffeine is a commonly used drug that is metabolized predominantly by a component of the hepatic microsomal mixed-function oxidase complex, known as cytochrome P-448. Therefore the elimination of caffeine given orally was studied in normal volunteers after receiving either orange juice or 0.8 gm/kg ethanol as a 25% solution in orange juice. Short-term administration of ethanol resulted in a significant decrease in the plasma clearance of caffeine from 96.6 +/- 13.4 ml/min to 60.7 +/- 10.5 (mean +/- S.E., p less than 0.05). There was also a corresponding significant increase in the elimination half-life of caffeine from 4.03 +/- 0.52 hr to 6.04 + 0.73 (mean + S.E., p less than 0.01). To determine whether the decrease in caffeine elimination was due to an inhibition of caffeine metabolism by ethanol or to an effect on caffeine absorption, caffeine disposition was studied in four healthy, mongrel dogs after intravenous administration. Each animal served as its own control. Caffeine clearance decreased significantly from a baseline value of 19.6 +/- 1.5 ml/min to 8.0 +/- 1.5 (mean +/- S.E., p less than 0.05) after administration of 3.0 gm/kg ethanol given orally 1 hr before intravenous caffeine injection. These results imply that short-term administration of ethanol inhibits the metabolism of caffeine, a predominantly cytochrome P-448-dependent substrate, in both man and dogs.

Adult↗
PubMed1981

Tissue distribution of caffeine in premature infants and in newborn and adult dogs.

Caffeine concentrations were measured in postmortem tissues of two premature infants who had received caffeine for the prevention of apnea. The distribution of caffeine was not uniform: Up to a 2.1-fold difference in caffeine concentrations existed among the various tissues in one infant and up tu a 4.3-fold difference in the other. This variability was only slightly reduced when caffeine concentrations were corrected for the water content of the respective tissues. Caffeine was also analyzed in tissues of newborn and adult dogs 3, 10, and 36 hr after single doses of caffeine (50 mg/kg IV). The decrease in caffeine concentrations was slower in the puppy than in the adult dog. The ratio tissue water caffeine/plasma water caffeine decreased with time after administration of this drug: It ranged between 0.9 and 1.1 at 3 hr and between 0.5 and 1.0 at 10 hr in adult dogs, and it varied from 0.8 to 1.3 at 3 hr and from 0.5 to 0.8 at 36 hr in puppies. Greater caffeine concentrations in newborn than in adult tissues following a given dose are consistent with the known slow elimination rate of caffeine in the young organism.

Aging↗
PubMed1995

Does adenosine receptor blockade mediate caffeine-induced rotational behavior?

Caffeine, a competitive antagonist at adenosine receptors, produces contralateral turning in rats with unilateral 6-hydroxydopamine-induced lesions of the nigrostriatal pathway. Adenosine A2a and dopamine D2 receptors are negatively coupled in the striatum; blockade of these adenosine receptors is a possible mechanism of caffeine-induced rotational behavior. The present study had three objectives: 1) to evaluate the role of adenosine receptor blockade in the rotational behavior elicited by caffeine in rats. This was done by determining the dose-response functions for turning behavior induced by caffeine, by six other methylxanthine adenosine antagonists and by CGS 15943 [9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo[1,5- c]quinazolin-5-imine], a potent nonxanthine adenosine antagonist; 2) to determine if selective dopamine receptor antagonist block caffeine-induced rotational behavior; and 3) to determine if tolerance develops to caffeine-induced rotational behavior as it does to caffeine-induced stimulation of locomotor activity. Theophylline, paraxanthine, caffeine and beta-hydroxytheophylline, in that order of potency, produced contralateral turning, but 3-isobutyl-1-methylxanthine, 8-chlorotheophylline, theobromine and CGS 15943 did not. Caffeine-induced turning was blocked by eticlopride (dopamine D2 antagonist), but not by SCH 23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H- 3-benzazepine] (dopamine D1 receptor antagonist), suggesting involvement of the dopamine D2 receptor. Rats treated chronically with an p.o. caffeine solution (75 mg/kg/day average intake) were tolerant to turning induced by caffeine and cross-tolerant to turning induced by theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Effects of coffee and caffeine on fertility, reproduction, lactation, and development. Review of human and animal data].

In the present review, we have examined the effects of coffee ingestion on fertility, reproduction, lactation and development. The potential effects of coffee consumption on fertility, spontaneous abortion and prematurity are not clearly established but appear to be quite limited. In rodents, caffeine can induce malformations but this effect appears in general at doses never encountered in humans. Indeed, as soon as the quantity of caffeine is divided over the day, as is the case for human consumption, the teratogenic effect of caffeine disappears in rodents. Coffee ingested during gestation induces a dose-dependent decrease in birth weight, but usually only when ingested amounts are high (i.e. more than 7 cups/day), whereas coffee has no effect at moderate doses. Caffeine consumption during gestation affects hematologic parameters of the new-born infant or rat. In animals, caffeine induces long-term consequences on sleep, locomotion, learning abilities, emotivity and anxiety, whereas, in children, the effects of early exposure to coffee and caffeine on behavior are not clearly established. The quantities of caffeine found in maternal milk vary with authors, but it appears clearly that caffeine does not change maternal milk composition and has a tendency to stimule milk production. In conclusion to this review, it appears that maternal coffee or caffeine consumption during gestation and/or lactation does not seem to have measurable consequences on the fetus of the newborn, as long as ingested quantities remain moderate. Therefore, pregnant mothers should be advised to limit their coffee and caffeine intake to 300 mg caffeine/day (i.e. 2-3 cups of coffee or 2.5-3 l of coke) especially because of the increase of caffeine half-life during the third trimester of pregnancy and in the neonate.

Animals↗
PubMed1993

Caffeine withdrawal: apparent heterologous sensitization to adenosine and prostacyclin actions in human platelets.

Chronic exposure to caffeine increases the number of adenosine receptors (up-regulation) but these observations have been mostly limited to animal models that study A1 adenosine receptors. The regulation of adenosine receptors by caffeine in humans and, in particular A2 receptors, remains largely unexplored. The purpose of this study was to test the hypothesis that withdrawal from chronic caffeine administration results in up-regulation of A2 adenosine receptors in humans. The authors also wanted to determine whether caffeine induces homologous or heterologous up-regulation. Caffeine 250 mg three times daily was given orally to a total of 19 normal volunteers for 7 days. Platelets were obtained at base line and 12 and 60 hr after the last dose of caffeine and the antiaggregation responses to adenosine and prostacyclin receptors were evaluated ex vivo. Plasma caffeine levels remained elevated at 22 microM 12 hr after the last dose but decreased to 0.6 microM at 60 hr. Adenosine receptor activation with the agonist 5'-N-ethylcarboxamidoadenosine and prostacyclin receptor activation with iloprost or prostaglandin E1 produced a greater antiaggregation effect at 60 hr postcaffeine. Increased responsiveness to both receptors could also be demonstrated at 12 hr after removal of caffeine by washing the platelets. Sensitization to the actions of prostacyclin, however, was reversed if caffeine was added ex vivo. These results support the hypothesis that chronic caffeine exposure induces heterologous up-regulation of adenosine and prostacyclin receptors in humans and implies that endogenous adenosine normally modulates platelet adenosine receptors in vivo. These findings may be relevant to the caffeine withdrawal syndrome observed in humans.

Adenosine↗
PubMed1993

Caffeine treatment and withdrawal in mice: relationships between dosage, concentrations, locomotor activity and A1 adenosine receptor binding.

Relationships between caffeine dose, methylxanthine tissue concentrations, adenosine receptor binding and locomotor activity were examined in CD-1 mice. A method of caffeine infusion via s.c. pumps provided constant steady-state methylxanthine concentrations. Mice receiving caffeine doses of 97 mg/kg/day (with mean plasma concentration of 2.7 micrograms/ml) demonstrated motor activity depression for 6 days after pump implantation (vs. vehicle-treated controls). Mice receiving caffeine doses of 194 mg/kg/day (mean plasma concentration of 7.1 micrograms/ml) demonstrated motor stimulation 4 and 24 hr after implantation. Mice receiving this dose for 6 days developed motor depression. A reduction in the stimulant effects of acute caffeine (20 mg/kg i.p.) was found in mice receiving caffeine infusions (194 mg/kg/day for 6 days) as compared to those receiving vehicle infusions, suggestive of drug tolerance. These dose- and time-dependent behavioral effects during caffeine-infusion were associated with decreases between 20 and 69% in specific binding of A1 adenosine radioligand 1,3-[3H]dipropyl-8-cyclopentylxanthine in vivo. Behavioral alterations during caffeine infusion appear to be mediated by A1 adenosine receptor occupancy. Increasing motor depression developed on days 1 and 2 after pump removal with values returning to control levels by days 4 and 6. Behavioral alterations were associated with in vivo binding increases of 98 and 324%, respectively, and a return to control values on days 4 and 6. In vivo binding alterations were not associated with ex vivo A1 receptor binding changes. Caffeine tolerance and withdrawal effects in this animal model appear to be mediated by chronic occupancy of A1 adenosine receptors. The behavioral and in vivo receptor binding alterations observed after caffeine discontinuation follow a time course similar to caffeine withdrawal in humans.

Animals↗
PubMed1996

Caffeine clearance by two point analysis: a measure of liver function in chronic liver disease.

This study attempted to compare the pharmacokinetic parameters of caffeine in patients with chronic liver disease and in normal subjects and to define the two sampling times which are suitable for determining caffeine clearance in these patients. Ten decompensated and eight compensated cirrhotic patients, and nine patients with chronic hepatitis were given a 3.5 mg/kg single oral dose of caffeine, followed by measurement of serum caffeine concentrations at 0, 30, 60, 90 minutes and 3, 5, 10, 24 and 36 hours using the HPLC technique. Caffeine clearance and its elimination rate constant in the decompensated cirrhotic patients were significantly lower than those in the compensated cirrhotic patients and much lower than in normal subjects (p > 0.01). Caffeine clearance in chronic hepatitis patients was also significantly lower than in normal subjects. The volumes of distribution of caffeine in compensated and decompensated cirrhotic patients and normal subjects were significantly different. There was also a significant difference between normal subjects and the chronic hepatitis group. Serum caffeine clearance showed a good correlation with Child Pugh's score at r = -0.788. Two sampling times within 10 to 24 hours after oral dose of caffeine served as the best sampling points for determination of caffeine clearance by the simple equation; Cl = kel approximately Vd (Vd is a fixed value in each group). It was clearly shown that caffeine clearance, calculated by two point analysis, would be a simple and useful method for measuring liver function in chronic liver disease.

Adult↗
PubMed1997

Functional antagonism of the caffeine-discriminative stimulus by triazolam in humans.

Six healthy male volunteers (aged 21-31 yr) were trained to discriminate between the methylxanthine caffeine (320 mg/70 kg, p.o.; e.g. drug A) and placebo (drug B). Then dose-effect curves were determined for triazolam (0.1-0.56 mg/70 kg), alone and in combination with the caffeine training dose (n = 6), buspirone (1.0-32.0 mg/70 kg), alone and in combination with the caffeine training dose (n = 4), and caffeine (56-560 mg/70 kg), alone and in combination with a selected dose of triazolam (n = 5). Triazolam blocked the discriminative effects of the caffeine training dose in a dose-related manner in five out of six subjects; whereas buspirone did so in only one out of four subjects. Different doses of caffeine alone generally produced dose-related increases in caffeine-appropriate responding; when administered concomitantly with triazolam, the caffeine dose-effect curve shifted significantly to the right. Triazolam and caffeine, but not buspirone and caffeine, generally produced significant interactions on several self-report and psychomotor performance measures. These results indicate that, at the doses tested, the caffeine discriminative stimulus can be blocked, at least partly by triazolam, but not by buspirone, which is consistent with the pharmacological actions of these compounds.

Adult↗
PubMed2005

Habitual caffeine intake and the risk of hypertension in women.

CONTEXT: Caffeine acutely increases blood pressure, but the association between habitual consumption of caffeinated beverages and incident hypertension is uncertain. OBJECTIVE: To examine the association between caffeine intake and incident hypertension in women. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study conducted in the Nurses' Health Studies (NHSs) I and II of 155,594 US women free from physician-diagnosed hypertension followed up over 12 years (1990-1991 to 2002-2003 questionnaires). Caffeine intake and possible confounders were ascertained from regularly administered questionnaires. We also tested the associations with types of caffeinated beverages. MAIN OUTCOME MEASURE: Incident physician-diagnosed hypertension. RESULTS: During follow-up, 19,541 incident cases of physician-diagnosed hypertension were reported in NHS I and 13,536 in NHS II. In both cohorts, no linear association between caffeine consumption and risk of incident hypertension was observed after multivariate adjustment (NHS I, P for trend = .29; NHS II, P for trend = .53). Using categorical analysis, an inverse U-shaped association between caffeine consumption and incident hypertension was found. Compared with participants in the lowest quintile of caffeine consumption, those in the third quintile had a 13% and 12% increased risk of hypertension, respectively (95% confidence interval in NHS I, 8%-18%; in NHS II, 6%-18%). When studying individual classes of caffeinated beverages, habitual coffee consumption was not associated with increased risk of hypertension. By contrast, consumption of cola beverages was associated with an increased risk of hypertension, independent of whether it was sugared or diet cola (P for trend <.001). CONCLUSION: No linear association between caffeine consumption and incident hypertension was found. Even though habitual coffee consumption was not associated with an increased risk of hypertension, consumption of sugared or diet cola was associated with it. Further research to elucidate the role of cola beverages in hypertension is warranted.

Caffeine↗