Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Chlorobutanol”

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 19 recordsLinked to original sources
PubMed2000

Effects of chlorobutanol on primary and secondary endings of isolated cat muscle spindles.

The effects of the preservative chlorobutanol on primary and secondary endings of muscle spindles isolated from the tenuissimus muscle of the cat were investigated in this study. Chlorobutanol was applied to the bathing solution in final concentrations of between 10 and 100 microg/ml. It induced a reversible and dose dependent decrease in the discharge frequency of both types of ending without any visible length change in the sensory region of the receptor. The initial activity, the peak dynamic discharge, the maximum static discharge value and the final static discharge value were evaluated from an ending's discharge pattern obtained during ramp-and-hold stretches. These four basic discharge frequencies decreased in parallel with increasing concentrations of chlorobutanol. Their sensitivities to chlorobutanol were similar (mean values: -0.11 to -0.29 imp/s per microg/ml chlorobutanol) and were independent of the amplitude of stretch. The dynamic response and the static response of both primary and secondary endings remained unchanged, indicating that the sensitivity of the spindle to stretch was not influenced by chlorobutanol. Chlorobutanol also reduced the discharge activity of the muscle spindle afferents during sinusoidal stretches. The amplitude of the receptor potential (AC component) remained unchanged under chlorobutanol. With the available recording technique it was not possible to measure slow shifts of the membrane potential. However, a hyperpolarization of the ending's membrane might explain why the afferent discharge frequency is reduced by chlorobutanol. The calcium dynamics of the spindle do not appear to be altered by CB, as the effect exerted on the afferent discharge by a change in the extracellular calcium concentration and a blockage of calcium channels was different from the CB effect. As the inhibitory effect of CB was reduced by ouabain, it is possible that CB activates the electrogenic Na/K pump or affects a mechanism that is closely related to the activity of the pump. The properties of the axonal membrane appear not to be altered, as chlorobutanol did not change the shape of action potentials.

Action Potentials↗
PubMedDate not supplied

Effect of chlorobutanol on Limulus ventral photoreceptor latency: a model of a two component latent period.

Chlorobutanol (1,1,1-trichlor-2-methyl-2-propanol) decreases the duration of the latent period of Limulus ventral eye receptor potentials. This effect is both concentration and intensity dependent. Between 0.05 and 1 mM chlorobutanol in sea water the extent of latency shortening effect of chlorobutanol linear function of the logarithm of the chlorobutanol concentration. The latency shortening effect of chlorobutanol diminishes with decreasing intensity of stimulation and virtually disappears at intensities just exceeding threshold. These results are explained by postulating that the latent period is composed of two processes only one of which is sensitive to chlorobutanol and, further, that the duration of the chlorobutanol-sensitive process is not appreciably affected by the stimulating intensity. This model of a two component latent period may be tested experimentally. In several experiments prolonged exposure of ventral photoreceptor cells to chlorobutanol coupled with a short exposure to calcium deficient sea water produced a collapse of the receptor potential followed by a slow recovery after returning to perfusion with normal sea water. During the recovery a slow, low amplitude positive wave exists which has been tentatively called a prepotential.

Animals↗
PubMed1990

Chlorobutanol, a preservative of desmopressin, inhibits human platelet aggregation and release in vitro.

Therapeutic preparations of desmopressin for parenteral use contain the preservative chlorobutanol (5 mg/ml). We show here that chlorobutanol is a potent inhibitor of platelet aggregation and release. It exhibited a significant inhibitory activity toward several aggregation inducers in a concentration- and time-dependent manner. Thromboxane B2 formation, ATP release, and elevation of cytosolic free calcium caused by collagen, ADP, epinephrine, arachidonic acid and thrombin respectively were markedly inhibited by chlorobutanol. Chlorobutanol had no effect on elastase-treated platelets and its antiplatelet effect could be reversed. It is concluded that the antiplatelet effect of chlorobutanol is mainly due to its inhibition on the arachidonic acid pathway but it is unlikely to have a nonspecific toxic effect. This antiplatelet effect of chlorobutanol suggests that desmopressin, when administered for improving hemostasis, should not contain chlorobutanol as a preservative.

Adenosine Triphosphate↗
PubMed1993

Dual effects of chlorobutanol on secretory response and intracellular Ca2+ dynamics in isolated pancreatic acini of the rat.

1. The effects of chlorobutanol, a widely used drug preservative, on exocrine response and intracellular Ca2+ dynamics were examined in isolated pancreatic acini of the rat. 2. Chlorobutanol (1 mg ml-1) markedly inhibited the secretory response to cholecystokinin octapeptide (CCK-8), carbamylcholine chloride (carbachol), or sodium fluoride, a direct G-protein activator. However, chlorobutanol itself induced a maximal release of amylase when the dose was increased to 4 mg ml-1. 3. An oscillatory fluctuation of cytoplasmic Ca2+ concentration, [Ca2+]c, induced by 5 pM CCK-8 or 0.3 microM carbachol was totally abolished in the presence of 1 mg ml-1 chlorobutanol. 4. A biphasic change in [Ca2+]c induced by 100 pM CCK-8, a rapid rise followed by a gradual decay, was transformed to an oscillatory fluctuation by the preservative. 5. Chlorobutanol inhibited 13 pM [125I]-CCK-8 or 0.5 nM [3H]-methylscopolamine chloride binding to the acinar cells in a dose-dependent manner. 6. These results indicate that chlorobutanol produces discernible pharmacological effects on the secretory response in rat pancreatic acinar cells through changes in the Ca2+ dynamics. Possible sites of action could be at a binding process of secretagogues to their receptors, at an activation process of a G-protein located in the plasma membrane, or at the processes following G-protein activation. However, the possibility that the preservative may distort the Ca(2+)-transport function of the plasma membrane or the membrane of intracellular organella, especially Ca(2+)-sequestering pools, cannot be excluded.

Amylases↗
PubMed1976

Effects of chlorobutanol and bradykinin on myocardial excitation.

The negative inotropic effect of a commonly used formulation of bradykinin (Sandoz BRS-640) was found to be due to chlorobutanol, a constituent of the preparation. Solutions containing up to 100 mug of crystalline bradykinin/ml had no effect on tension or action-potential shape. Chlorobutanol (500 mug/ml) caused a 30% decrease in contraction amplitude and a 20% increase in action-potential duration. Chlorobutanol lowered conduction velocity and induced conduction failure and automaticity within isolated ventricular muscle strips. Chlorobutanol affected neither positive nor negative treppe. We conclude that bradykinin has no direct action on toad, frog, or rat myocardium. However, chlorobutanol does have direct effects on myocardial cells, acting on the cell membrane and decreasing isometric tension produced by the heart.

Acetylcholine↗
PubMed1996

Chlorobutanol toxicity.

Although chlorobutanol is available in a large number of preparations, the incidence of toxicity appears to be low. However, with continued exposure to high-dose chlorobutanol, significant toxicity may occur. It seems prudent to use caution in the continued administration of products containing chlorobutanol. The lack of pharmacokinetic data warrant that extra care be used when administering chlorobutanol-containing products to patients with hepatic or renal dysfunction. Patients should be monitored for possible increased somnolence, alterations in speech pattern, dysarthria, and hemodynamic changes. Chlorobutanol toxicity should be ruled out by serum analysis if the patient exhibits any of the above reactions.

Adult↗
PubMedDate not supplied

Interaction of light and chlorobutanol on Limulus ventral photoreceptor potential latency.

Exposure of Limulus ventral photoreceptors to light or to chlorobutanol produces a shortening of the latent period of the receptor potential. The latency shortening effect of chlorobutanol (0.5 mM) is maximal in dark adapted photoreceptors and decreases progressively as the level of light adaptation increases. At the highest usable levels of light adaptation, the latencies of receptor potentials from cells exposed only to sea water containing chlorobutanol were virtually identical. This confluence of the latent periods suggests that light and chlorobutanol may affect the same component of the latent period.

Animals↗
PubMed1994

Acute effects of chlorobutanol- or benzalkonium chloride-containing artificial tears on the surface features of rabbit corneal epithelial cells.

I examined the epithelial surface, by high resolution scanning electron microscopy, after its recovery from the instillation of artificial tears containing chlorobutanol or benzalkonium chloride. Is the mild epithelial surface compromise observed after occasional use of a chlorobutanol-containing artificial tear more substantial after use of a benzalkonium-containing artificial tear? Two drops of a chlorobutanol- or benzalkonium chloride-containing artificial tear were instilled into the right eye of 6 female gray rabbits (2 kg) at 9:00 p.m. and 9:00 a.m. At the same time six control animals received no eyedrops. All animals were euthanized at 3:00 p.m. and the central region of the corneal epithelium quantitatively assessed using a digitizer pad/computer system. There were up to 5% exfoliating cells evident at the ocular surface in treated rabbits but with no difference between the two products. Controls had no cell exfoliation (< 0.5%). The distribution of surface areas of the squamous cells in the treated eyes was shifted to slightly larger values than in the controls after use of the chlorobutanol-containing product but the number of epithelial cell craters/cell was unchanged from that of the controls. Cell surface areas were shifted to significantly smaller values than controls after use of the benzalkonium chloride-containing product and there were much fewer epithelial cell craters/cell. The results reveal differences in the effects of preservative-containing artificial tears on the squamous cells of the corneal epithelium in a clinically relevant situation.

Administration, Topical↗
PubMed1983

Analysis of chlorobutanol in ophthalmic ointments and aqueous solutions by reverse-phase high-performance liquid chromatography.

A reverse-phase high-performance liquid chromatographic assay for chlorobutanol was developed and found suitable for the routine analysis of ophthalmic ointments and aqueous solutions. The method utilized a column packed with 10-microns octadecylsilane with a mobile phase of methanol-water (50:50). Peak detection was by UV absorption at 210 nm. In this chromatographic system, chlorobutanol had a capacity factor (K') of 4.1. Standard curves obtained in the presence of ointment vehicle containing an aminoglycoside were linear, intercepted at zero, and averaged 99.4% recovery. Degradation studies indicated that the method was stability indicating. The analytical results for a complete experimental ophthalmic ointment and an aqueous ophthalmic diluent are presented. This high-performance liquid chromatographic method of analysis represents an alternative to GC procedures for determining chlorobutanol.

Chlorobutanol↗
PubMed1984

Rapid determination of chlorobutanol in milk by glass capillary gas chromatography.

A rapid method for the determination of chlorobutanol(1,1,1-trichloro-2-methylpropan-2-ol) in milk is described. The method is based on a steam-distillation solvent-extraction technique and a quantitative determination of chlorobutanol by gas chromatography using a glass-capillary column coated with Carbowax 20M and 2,2,2-trichloroethanol as internal standard. The detection limit is 1 pg and recoveries of chlorobutanol are between 93 und 99%. Fifty-two milk samples have been analysed.

Animals↗
PubMedDate not supplied

The latent period of the Limulus lateral eye receptor potential: action of chlorobutanol.

Excised lateral eye retinular cells of Limulus polyphemus exposed to chlorobutanol were examined using microelectrode techniques. The effects observed were: (1) a marked shortening of the receptor potential latent period; (2) a decrease in the effective input resistance of retinular cells to hyperpolariziog currents; and (3) a reduction in magnitude of retinular cell receptor and membrane potential. The magnitude of the changes were concentration dependent and reversible and were only produced by chlorobutanol and closely related compounds. Chlorobutanol does not alter the sodium permeability of the receptor cell membrane but it may increase the rate of the process or processes occurring during the latent period of the receptor potential.

Animals↗
PubMed1995

Determination of chlorobutanol in mouse serum, urine and embryos by capillary gas chromatography with electron capture detection.

A sensitive and specific method for the determination of chlorobutanol (1,1,1-trichloro-2-methyl-2-propanol) in mouse serum, urine, and embryos by capillary gas chromatography with electron capture detection is described. For sample preparation n-hexane was used to extract chlorobutanol and the internal standard 2,2,2-trichloroethanol (TCE) from each matrix. Following extraction chromatographic separation of the samples was achieved with a fused-silica capillary column (30 m x 0.25 mm I.D., 0.25 micron film thickness). The method as described has the required sensitivity to quantitate chlorobutanol in individual embryos following administration of a single oral dose of the drug to a pregnant mouse. The limit of detection was 1 pg on column and the detector response was linear from 1 to 100 micrograms/ml for serum, 0.2 to 20 micrograms/ml for urine, and 1 to 10 ng/embryo.

Animals↗
PubMed1980

Effect of pH, chlorobutanol, cysteine hydrochloride, ethylenediaminetetraacetic acid, propylene glycol, sodium metabisulfite, and sodium sulfite on furosemide stability in aqueous solutions.

A study was conducted to determine the effects of pH, two antioxidants, a chelating agent, a preservative, and propylene glycol on furosemide stability. Aqueous solutions of furosemide containing 10% alcohol (v/v) were prepared in phosphate buffers with various pH values (5, 6, and 9) whose ionic strength was adjusted to 0.1 M with potassium chloride. Some solutions contained chlorobutanol, ethylenediaminetetraacetic acid, or sodium metabisulfite. Another set of aqueous solutions contained phosphate buffer (0.1 M), alcohol (10% v/v), and propylene glycol (40% v/v) with or without cysteine hydrochloride, ethylenediaminetetraacetic acid, and sodium sulfite. The solutions were divided into two parts, stored at 24 and 50 degrees, and assayed frequently using a previously developed high-pressure liquid chromatographic procedure. At the lowest pH value (pH 5), furosemide appeared to be very unstable. Cysteine hydrochloride, ethylenediaminetetraacetic acid, and sodium sulfite failed to improve the stability of furosemide. Chlorobutanol and sodium metabisulfite had an adverse effect on the stability, probably due to the fact that they decreased the pH of the solution. The pH value appears to be the only critical factor for the stability of furosemide. Buffered solutions containing propylene glycol were very stable at both temperatures for 170 days, and they tasted good.

Chemical Phenomena↗
PubMed1993

Embryotoxic effects of chlorobutanol in cultured mouse embryos.

Chlorobutanol (CB) is a commonly used preservative which is added to numerous pharmaceutical preparations, and it is the active ingredient in certain oral sedatives and topical anesthetics. Chlorobutanol has demonstrated adverse effects in adult tissues, but CB has not been previously investigated for its effect on the developing whole embryo. The method of whole-embryo culture was used in this study to expose mouse embryos during two stages of organogenesis to CB at final concentrations of 0 (control), 10, 25, 50, 100, and 200 micrograms/ml. Embryos were evaluated for heart rate (HR), malformations, and somite number, and embryos and visceral yolk sacs (VYSs) were assayed for total protein content as a measure of overall growth. Neurulating (3-6 somite) embryos were malformed and growth retarded by exposure to CB concentrations > or = 25 micrograms/ml, with decreased VYS growth at > or = 50 micrograms/ml and decreased HR at > or = 100 micrograms/ml CB. Early limb-bud stage (20-25 somite) embryos were malformed at CB concentrations > or = 50 micrograms/ml and growth retarded at > or = 100 micrograms/ml, with decreased VYS growth at 200 micrograms/ml and decreased HR at > or = 100 micrograms/ml CB. Thus, CB produces dysmorphogenesis in mouse embryos in vitro, and neurulating embryos are somewhat less sensitive than early limb-bud stage embryos. The concentrations of CB that interfere with normal embryonic development are within the range of human blood levels measured following multiple doses of CB. Preparations containing CB should be used with caution during pregnancy, particularly when repeated dosing may allow accumulation of CB to potentially embryotoxic levels.

Abnormalities, Drug-Induced↗
PubMed1989

Cytotoxic effects of benzalkonium chloride and chlorobutanol on human corneal epithelial cells in vitro.

By exposing primary cultures of human corneal epithelial cells to a single dose of either benzalkonium chloride or chlorobutanol, evaluated the cytotoxicity of these two preservatives which are commonly used in artificial tear solutions and other topical ophthalmic medications. Control and experimental cultures were analyzed by continuous time-lapse videomicrographic recordings as well as by sequential phase-contrast microscopy. Both benzalkonium chloride at a concentration of 0.01% and chlorobutanol at 0.5% caused immediate cessation of normal cytokinesis and mitotic activity, and epithelial cells degenerated within two hours and eight hours, respectively.

Benzalkonium Compounds↗
PubMed1997

Chlorobutanol: maternal serum levels and placental transfer in the mouse.

Chlorobutanol (CB) is a pharmaceutical preservative and the active ingredient in certain sedatives and anesthetics and produces adverse effects in adult tissues and mouse embryos in vitro. Chlorobutanol is slowly eliminated in humans, but little is known about its serum levels in other species or placental transfer in any species. Pregnant mice gavaged with 80 mg CB/kg on gestational day (gd) 9.5 provided serum at 10 min to 36 h post-dosing for a time course study. Additional mice gavaged with 0, 8, 40 or 80 mg CB/kg on gd 9.5 provided maternal serum and embryos 2 h post-dosing for a placental transfer study, and CB levels were measured using capillary gas chromatography with electron capture detection. Dosing with 80 mg CB/kg produced maternal serum levels between 30.8 micrograms/mL (10 min) and < 1 microgram/mL (36 h), with a half-life of 7.45 h. Embryonic CB levels increased with maternal dose and were correlated with maternal serum levels. Serum levels of CB in the mouse appeared to follow a time course similar to humans, with rapid absorption and slow elimination. Placental transfer, as demonstrated here in the mouse, may allow embryonic accumulation of CB to potentially toxic levels.

Administration, Oral↗
PubMed1992

Twice-daily use of a chlorobutanol-preserved artificial tear on rabbit corneal epithelium assessed by scanning electron microscopy.

Female pigmented rabbits received two drops of a chlorobutanol 0.5%-preserved, polyvinyl alcohol-based artificial tear at 21.00 h and 09.00 h for 1, 2, 3, 6 or 12 consecutive days. The animals were killed at 15.00, 6 h after the last treatment. Scanning electron microscopy of the corneal epithelial surface at x 200 magnification revealed only occasional cell exfoliation averaging < 8% of the surface analysed at central, mid-peripheral and peripheral sites, showing minimal cytotoxic effects. The level of exfoliation was maximal after 2 to 3 days treatment and then returned to close to zero, so the eye adapts to repeated use of the artificial tears. Evaluation of the surface microplicae of the cells at x 15,000 indicated subtle, but distinct, changes in what might be the mucus material associated with the cell surface, especially after 2 and 3 days treatment.

Animals↗
PubMed1975

Chlorobutanol poisoning. Report of a fatal case.

A fatal chlorobutanol intoxication is reported and a gas chromatographic method for the determination of this drug in human fluids and tissues is described. Analytical findings for blood, urine, stomach contents, bile, liver, kidney, spleen, and brain are reported.

Chromatography, Gas↗