Effect of naloxone on ethanol- and pentobarbital-induced narcosis

1982 ◽  
Vol 60 (10) ◽  
pp. 1315-1318 ◽  
Author(s):  
J. M. Khanna ◽  
J. M. Mayer ◽  
H. Kalant ◽  
G. Shah
Keyword(s):  
Sleep Duration ◽  
Low Doses ◽  
Small Reduction ◽  
High Doses ◽  
Higher Doses ◽  
Convulsant Effect

Single or repeated subcutaneous administrations of naloxone in doses of up to 4 mg∙kg−1 did not alter the time for onset or the duration of ethanol- or pentobarbital-induced narcosis in rats. An increase in the naloxone dosage to 50 mg∙kg−1 s.c. resulted in a small reduction of ethanol-induced sleep duration. Repeated i.p. or i.v. administrations of much higher doses of naloxone (300–400 mg∙kg−1 and 120–180 mg∙kg−1, respectively) did produce significant reductions in ethanol-induced narcosis. However, similar naloxone doses, when administered alone, i.v., had marked convulsant effect. It appears that naloxone, in low doses, is not an effective antidote for narcosis caused by ethanol or pentobarbital at the ethanol and pentobarbital doses tested, whereas the antagonism of ethanol-induced sleep by high doses of naloxone may be due to the analeptic action of this drug.

Effect of methacholine chloride on rheology and transport of canine tracheal mucus

1979 ◽  
Vol 47 (1) ◽  
pp. 26-31 ◽  
Author(s):  
M. King ◽  
N. Viires
Keyword(s):  
Mechanical Properties ◽  
Elastic Modulus ◽  
Base Line ◽  
Low Doses ◽  
Mucociliary Transport ◽  
Frog Palate ◽  
High Doses ◽  
Tracheal Mucus ◽  
Higher Doses ◽  
Cytology Brush

The effect of methacholine chloride (M) on tracheal mucus was investigated in three conscious tracheostomized dogs. Aerosols of M in concentrations of 2--32 mg/ml were delivered intratracheally for 1 min. Mucus was sampled with a cytology brush at 2 min postchallenge and at irregular intervals thereafter. The mechanical properties of each sample were determined in the magnetic microrheometer, and correlated with mucociliary transportability as assayed by the frog palate technique. With high doses of M, there was an increase in volume of secretion collected per unit time. The elastic modulus (G′) at 2 min postchallenge went up (to 1.5 x 2.3 x control for 16 and 32 mg/ml, respectively) then fell below control before returning to base line after 30 or 45 min. With low doses of M (2--8 mg/ml) the secretion rate was also above control, but only a decrease in G′ (to 0.54 x control) was observed. The decrease in G′ at low doses did not significantly alter the frog palate transport rate; however, the increase at higher doses did impede mucociliary transport.

Morphology-Property Relationships in EPDM-Polybutadiene Blends

1982 ◽  
Vol 55 (1) ◽  
pp. 151-160 ◽  
Author(s):  
Gary R. Hamed
Keyword(s):  
Mechanical Properties ◽  
Particle Size ◽  
Interfacial Adhesion ◽  
Pure Component ◽  
Dispersed Phase ◽  
Minor Effect ◽  
Low Doses ◽  
High Doses ◽  
A Minor ◽  
Higher Doses

Abstract When mixing EPDM and BR in the Brabender a heterogeneous blend results; the dispersed phase is first sheared into fibrous strands and then broken down into micron sized particles. At low doses of irradiation, the morphology of the blend only has a minor effect on the energy to break, whereas at high doses the Eb may increase by a factor of three as the dispersed particle size is reduced from the 100 micron range. The Eb of the blend is the weight-average of the two pure components at low doses (independent of morphology), but is greater than either pure component at higher doses. Interfacial adhesion may play a key role in determining the mechanical properties in rubbery blends.

Mechanism of Action of Trazodone: a Multifunctional Drug

CNS Spectrums ◽  
2009 ◽  
Vol 14 (10) ◽  
pp. 536-546 ◽  
Author(s):  
Stephen M. Stahl
Keyword(s):  
Controlled Release ◽  
Adrenergic Receptors ◽  
Low Dose ◽  
Low Doses ◽  
Release Formulation ◽  
Therapeutic Mechanism ◽  
High Doses ◽  
Pharmacologic Actions ◽  
Dose Dependent ◽  
Higher Doses

Multifunctional drugs are those with more than one therapeutic mechanism. Trazodone is a multifunctional drug with dose-dependent pharmacologic actions. That is, it has hypnotic actions at low doses due to blockade of 5-HT2A receptors, as well as H1 histamine receptors and α1 adrenergic receptors. Higher doses recruit the blockade of the serotonin transporter (SERT) and turn trazodone into an antidepressant. Although trazodone has traditionally been used as a low dose hypnotic, a new controlled release formulation that has the potential to improve the tolerability of high doses may provide an opportunity to revisit this multifunctional drug as an antidepressant as well.

Involvement of 5-Hydroxytryptamine in Platelet Aggregation In Vivo in Rats and Guinea Pigs

1989 ◽  
Vol 61 (03) ◽  
pp. 463-467 ◽  
Author(s):  
G M Smith
Keyword(s):  
Platelet Count ◽  
Guinea Pigs ◽  
Platelet Adhesion ◽  
Adenosine Diphosphate ◽  
Rate Of Return ◽  
Low Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Rat Platelets

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs

ANTAGONISTIC ACTION OF NORETHYNODREL ON THE TESTOSTERONE-DEPENDENT PROCESS OF FRUCTOSE FORMATION IN MOUSE SEX ACCESSORY ORGANS

1966 ◽  
Vol 51 (2) ◽  
pp. 224-230 ◽  
Author(s):  
John A. Thomas ◽  
Edward T. Knych
Keyword(s):  
Antagonistic Activity ◽  
Low Doses ◽  
Antagonistic Action ◽  
Dependent Process ◽  
High Doses

ABSTRACT Norethynodrel antagonized the fructose stimulating effects of exogenous testosterone in sex accessory organs of castrate mice. It was antiandrogenic at both low doses (50 μg) and high doses (400 μg) of testosterone. Norethindrone and ethisterone suppressed fructose formation in the testosterone-treated castrate mouse, but not as effectively as norethynodrel. Norethandrolone exerted no antagonistic activity.

scholarly journals Antifertility Actions of a-Chlorohydrin in the Male

1983 ◽  
Vol 36 (4) ◽  
pp. 333 ◽  
Author(s):  
A RJones
Keyword(s):  
Male Fertility ◽  
Human Sperm ◽  
Male Rat ◽  
Low Doses ◽  
Dose Regime ◽  
Male Contraceptive ◽  
The Past ◽  
High Doses ◽  
Species Specific ◽  
Daily Oral Administration

Non-steroidal chemicals that affect male fertility have been known for over 25 years but only one compound, oc-chlorohydrin, possesses most of the attributes of an ideal male contraceptive. In the male rat, for example, continuous daily oral administration of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn. Such a dose regime does not interfere with libido, is apparently not toxic and the action is specific towards mature sperm. Furthermore, the action of the compound is species-specific: it is effective in the rat, ram, boar, guinea pig, hamster,rhesus monkey and upon ejaculated human sperm but it is ineffective in the mouse and the rabbit. High doses of oc-chlorohydrin can be neurotoxic, nephrotoxic and, in rats, lead to prolonged or permanent infertility. However, the antifertility response and the toxicity of racemic oc-chlorohydrin may be due, respectively, to the separate enantiomers. No other antifertility chemical has been investigated to such an extent as oc-chlorohydrin; this article reviews the progress that has been achieved with oc-chlorohydrin during the past six years.

Effect of insulin on free fatty acid uptake by hepatocytes in the duck

1984 ◽  
Vol 102 (3) ◽  
pp. 381-386 ◽  
Author(s):  
R. Gross ◽  
P. Mialhe
Keyword(s):  
Fatty Acids ◽  
Growth Hormone ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Metabolism ◽  
Free Fatty Acids ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Low Doses ◽  
Higher Doses

ABSTRACT To elucidate the hypolipacidaemic effect of insulin in ducks, its action on the uptake of free fatty acids (FFA) by duck hepatocytes was determined. At low doses (10 mu./l) insulin stimulated FFA uptake. This effect was not observed with higher doses of insulin (20, 30 and 50 mu./l). Growth hormone at physiological concentrations and corticosterone (14·4 nmol/l) decreased basal activity, probably by reducing glucose metabolism and consequently α-glycerophosphate (α-GP) supply. Insulin was able to reverse the inhibition induced by GH and corticosterone on both FFA uptake and α-GP production. These results therefore suggest that the hypolipacidaemic effect of insulin may be partly mediated by its action on hepatic FFA uptake. J. Endocr. (1984) 102, 381–386

Gastrointestinal motor effects of erythromycin

1990 ◽  
Vol 259 (3) ◽  
pp. G355-G363 ◽  
Author(s):  
M. F. Otterson ◽  
S. K. Sarna
Keyword(s):  
Small Intestine ◽  
Cycle Length ◽  
Amplitude Ratio ◽  
Contractile Activity ◽  
Low Doses ◽  
Control Activity ◽  
Distal Small Intestine ◽  
Gastrointestinal Motor ◽  
High Doses ◽  
Motor Effects

We studied the small intestinal motor effects of oral and intravenous (iv) erythromycin in 10 conscious dogs. After control recordings with placebo, oral or iv erythromycin was given at 40% of the migrating motor complex (MMC) cycle. Recordings were made after administration until normal contractile activity had returned or 12 h postdrug administration. Low doses initiated a premature MMC. High doses, however, prolonged the MMC cycle length. Erythromycin reduced the MMC propagation velocity at all doses. Both oral and iv erythromycin induced amyogenesia. During this pattern, electrical control activity was obliterated in the proximal and destabilized in the distal small intestine. Erythromycin also increased the incidence of retrograde giant contractions (RGCs) and vomiting. These effects occurred within the first 2 h after oral and within the first 30 min after iv administration. The incidence of giant migrating contractions (GMCs) increased significantly from 5 to 12 h but not from 0 to 5 h after administration. The distance of origination of GMCs from the ileocolonic junction was significantly increased from 5 to 12 h. The amplitude ratio, duration, and velocity of migration of GMCs induced after erythromycin were similar to control values. Clusters of coordinated antral and duodenal contractions also occurred early after administration. Our findings suggest that erythromycin has multiple motor effects on the stomach and small intestine. Diarrhea, abdominal cramping, and vomiting associated with erythromycin may be related to increased incidence of GMCs and RGCs. Erythromycin has a biphasic effect on MMC cycle length, initiating premature MMCs at low doses and prolonging their cycle length at higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Decitabine: A Historical Review of the Development Process of an Epigenetic Drug

2020 ◽  
Vol 7 ◽  
Author(s):  
Cihan Zamur ◽  
Uğur Topal
Keyword(s):  
Development Process ◽  
Historical Review ◽  
Low Doses ◽  
Combination Therapies ◽  
Action Mechanism ◽  
Epigenetic Effect ◽  
Epigenetic Drug ◽  
Patient Responses ◽  
High Doses

Decitabine (5-aza-2p-deoxycytidine) is a hypomethylation agent with a double-action mechanism, these are the reactivation of silenced genes; exhibiting differentiation at low doses and showing cytotoxicity at high doses. Decitabine was used as a classic anticancer drug in the original studies in the 1980s, 1500 to 2500 mg/m2 per cycle was the maximum clinically tolerated dose. The dosage was reassessed after a better understanding of epigenetics in cancer and the role of decitabine in epigenetic (hypomethylation) therapy was obtained, in about 1/20th of the previous doses (i.e., 'optimal biological' doses modulating hypomethylation). It has been found that decitabine (100 to 150 mg / m2 per cycle) can be used in patients with myelodysplastic syndromes (MDS) and other myeloid tumors, with manageable side effects. Combination therapies which amplify the epigenetic effect of decitabine will most likely improve the patient responses and allow it to be used in the treatment of other malignancies.

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