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

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.

1983 ◽  
Vol 36 (4) ◽  
pp. 333 ◽  
Author(s):  
A RJones

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of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn.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.


1990 ◽  
Vol 259 (3) ◽  
pp. G355-G363 ◽  
Author(s):  
M. F. Otterson ◽  
S. K. Sarna

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)


2020 ◽  
Vol 7 ◽  
Author(s):  
Cihan Zamur ◽  
Uğur Topal

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.


Author(s):  
Nirmal Chandra Sukul ◽  
Tandra Sarkar ◽  
Atheni Konar ◽  
Anirban Sukul

Background: High dilutions of drugs, used in homeopathy, are usually applied by oral route or foliar spray. These dilutions first come in contact with membrane or circulating proteins. Ultra low doses of mercuric chloride, called potencies, promote activity of diastase or ?-amylase in terms of breakdown of starch, a polysaccharide into a disaccharide maltose in a cell-free medium in test tubes. Merc cor or HgCl2 in high doses inhibits the enzyme activity. Aims: To see (i) whether the high and ultra low dose effects of HgCl2 involve different binding sites of the enzyme and (ii) to find an explanation for the low dose effect of HgCl2 in spite of absence of its original molecules. Methodology: Merc cor mother tincture (147 mM HgCl2) in distilled water was used undiluted in this experiment. Merc cor 200c and 1000c were prepared from the mother tincture (MT) by successive dilution with water 1:100 followed by succussion in 200 and 1000 steps, respectively, and finally preserved in 90% EtOH. These potencies and blank 90% ethanol, were diluted with deionized, distilled (DD) water 1:1000 to minimize ethanol content in test solutions. Each test solution or control was mixed with the enzyme 1:10 just before experiment. The control consisted of DD water. An isothermal calorimetry (ITC) instrument was used to measure the interaction between soluble starch and ?-amylase mixed with each potency (200c/1000c) of Merc cor, its mother tincture, ethanol and control. ITC is a thermodynamic technique which helps in measuring directly very small amount of heat evolved during chemical reaction. Soluble starch 90 µM was injected into 300 µl of 15µM ?-amylase at 2 µl / injection. Twenty injections, one every 2 min, were given. The enzyme substrate interaction in terms of heat released (exothermic) or absorbed (endothermic) were monitored by the ITC instrument. All ITC measurements were calculated and analyzed statistically by an in-built software Origin 7. Results and discussion: The data are presented in figures. While Merc cor MT shows endothermic reaction, all its potencies, ethanol and water control show exothermic reactions. There is wide variation in enthalpy (?H), entropy (?S), binding constant (K) and Gibbs free energy change (?G) among the treatments with Merc cor MT, potencies, ethanol and also control. The results indicate that Merc cor MT and its potencies act on different binding sites of the enzyme. The variation in thermodynamic parameters suggest difference in binding interaction between the drug solutions and the enzyme. This in turn influences the enzyme substrate interaction as reported in earlier studies. The potencies are virtually water modified by the starting substance HgCl2. Conclusion: The mother tincture and potencies of mercuric chloride produce different effects on the enzyme substrate interaction. Potencies show wide variation in ?H, ?S, K and ?G values. It appears from the results that the drugs used in homeopathy produce dual action on proteins. At high doses they act on a binding site(s) but at ultra low doses they act on a different binding site(s). Proteins in an organism may serve as targets for initiation of action of homeopathic potencies.


2021 ◽  
Author(s):  
◽  
Anna-Lena Langen

<p>While 3,4-methylenedioxymethamphetamine (MDMA) shares many similarities with amphetamine, previous two choice drug discrimination procedures have shown that substitution between the two substances is inconsistent. Three choice drug discrimination procedures have revealed that MDMA can be discriminated from amphetamine, due to MDMA’s primary influence in releasing 5-HT. Neurochemical evidence had previously suggested that at doses >3.0mg/kg MDMA-induced dopamine (DA) release will increase significantly. In the current study rats were trained to discriminate MDMA from amphetamine and saline. As the dose of MDMA increased beyond the training dose (>1.5mg/kg) MDMA-appropriate responding decreased, while the proportion of amphetamine lever responding increased and eventually surpassed MDMA-appropriate responding at the highest dose (4.5mg/kg). This would indicate an important role for DA mediated influences in MDMA’s discriminative cue properties. Further evidence for this conclusion comes from tests with the D1 antagonist SCH23390 and the D2 antagonist eticlopride which attenuated this effect and also led to a nonsignificant increase in the proportion of saline lever responding. Subsequent tests with the 5-HT2c antagonist RS102221resulted in no significant dose dependent changes, but appeared to reduce MDMA-appropriate responding especially at the training dose. The current findings would suggest that low doses of MDMA are discriminable from amphetamine, however with increasing doses MDMA will be perceived as more “amphetamine-like”. These findings could suggest that at relatively high doses MDMA produces effects that are typically associated with dopamine-releasing drugs, such as high abuse potential.</p>


1979 ◽  
Vol 47 (1) ◽  
pp. 26-31 ◽  
Author(s):  
M. King ◽  
N. Viires

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.


1962 ◽  
Vol 202 (1) ◽  
pp. 97-102 ◽  
Author(s):  
David M. Worthen ◽  
Quentin N. Anderson ◽  
Lerner B. Hinshaw

To investigate the renal vascular changes induced by epinephrine, 21 isolated dog kidneys were perfused at constant pressure. Single injections and constant infusions of epinephrine were administered. Changes in blood and urine flow and arterial and intrarenal venous pressures were measured. Changes in renal volume were estimated with a kidney-weighing device, and determinations of cation concentrations were carried out. Data do not support the view that low doses of epinephrine cause diuresis. The previously reported afferent dilation and efferent constriction after epinephrine administration were not found in this investigation. Both increased and decreased urine flows were noted at low doses of epinephrine, whereas a fall in urine flow was consistently seen at high doses. The primary vascular effect of epinephrine is presumably on the afferent arteriole, since there was no consistent diuresis, no increase in kidney weight, a decrease in blood flow, and a decrease in filtration. Electrolyte excretion was not directly influenced by epinephrine. The pressure in the ureter was changed by epinephrine.


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