Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of S-alkanoyl and benzoyl derivatives of 3-mercaptopicolinic acid (3-MPA) was prepared and studied for hypoglycemic activity. Three alkanoyl derivatives (propionyl, pivaloyl, and 1-adamantanecarbonyl, 19-21) were prepared with increasing bulk around the thio ester bond. The benzoyl derivatives contained aromatic substituents chosen from a sigma-pi cluster chart so that the esters prepared had a wide range of electronic and solubility properties. In general, compounds with substituents which increased lipid solubility [p-chlorobenzoyl (4), p-trifluoromethylbenzoyl (6), and pivaloyl (20)] had the greatest potency at a dose of 300 mg/kg. Hydrolysis rates, measured at pH 6 and 8, indicated that in vivo breakdown to 3-MPA probably did not account for the observed hypoglycemic activity of the esters. 4, 6, and 20 were less potent than 3-MPA in comparative dose range studies.
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PMID:Synthesis and hypoglycemic activity of S-acyl derivatives of 3-mercaptopicolinic acid. 1 14

This study examines the effects of MPA (medroxyprogesterone acetate) on some of the hepatic enzymes of carbohydrate and lipid metabolism in the rat, and compares these with the effects of cortisol and saline. Levels of reduced nicotinamide adenine dinucleotide phosphate (NADPH) were also measured. Intact mature female Wistar rats with average initial weight of 200 gms were injected with MPA (mO mg/kg IM) once a week for 4 weeks and were sacrificed 3 to 5 days after the last injection. Hydrocortisone (Solu-Cortef [R]) 40 mg/kg IM were given to cortisol-treated animals twice daily for 7 days. The animals were sacrificed 2-4 hours after the last dose was given. Normal saline (0.2 mg. IM) was injected in control animals twice a day. The method of Jellinek, Amako, and Willman was used to analyze NADPH. Liver samples were assayed for various enzymatic activities such as phophofructokinase (PFK); pyruvate kinase (PK), glycerol-3-phosphate dehydrogenase (G3PD), "malic" enzyme (ME), and glucose-6-phosphate dehydrogenase (G6PD). The methods of Colowick and Kaplan were used in enzymatic analyses. Lipogenic stimulation by MPA is indicated by increased levels of G3PD and ME, both of which are implicated in lipogenesis, as well as by NADPH. PFK, PK, and G6PD were all unaffected by the MPA regimen, suggesting that elevation of ME and NADPH activities may reflect increased amino acid conservation. The enzymatic pattern of MPA treatment shows lipogenesis and protein conservation, while that of cortisol regimen shows significantly lower levels of ME, G3PD, and PRK.
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PMID:Some effects of medroxyprogesterone acetate on intermediary metabolism in rat liver. 2 59

We measured rat brain cortex PO2 (PtO2) with gold microelectrodes (tip diameter 5--10 micron) for up to 2 hours after 16 min of transient global brain ischemia with and without thiopental 90 mg/kg infused iv over 60 min beginning at 5 min postischemia. Seventeen rats were immobilized and mechanically ventilated on 1% halothane in oxygen with continuous monitoring of PtO2, ECG, end-expiratory CO2, rectal temperature, and arterial blood pressure. Global ischemia was induced by trimethaphan hypotension to an MAP of about 50 torr and a neck tourniquet inflated to 1500 torr. Postischemia, nine control rats (11 PtO2 measurements) were untreated and eight rats (8 PtO2 measurements) received thiopental 90 mg/kg. Preischemia, PtO2 values in both groups ranged from less than 5--70 torr with values of greatest frequency between 10 and 15 torr. Postischemia, PtO2 in control rats peaked at 45 +/- 8 (SEM) torr at 20 min. In thiopental treated rats, peak PtO2 was 24 +/- 6 torr at 10 min postischemia. Relative frequency histograms of PtO2 revealed that PtO2 in thiopental treated rats was lower (p less than 0.05) between 15 and 30 min postischemia. The magnitude of the decrease in PtO2 between 105 and 120 min postischemia appeared to correlate directly with the absolute preischemic value (i.e., the higher the preischemic PtO2, the greater the decrease in PtO2 postischemia). These results suggest that thiopental administered in large doses in early postischemia does not improve brain oxygenation secondary to a reduction in brain oxygen consumption. The relevance of the correlation between the magnitude of the fall in PtO2 postischemia and the magnitude of the preischemic value is discussed.
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PMID:Postischemic brain oxygenation with barbiturate therapy in rats. 3 43

Patients with two or more previous spontaneous second trimester abortions and vaginal cytology indicating a poor progestational response in current pregnancies were selected for treatment with Provera (medroxyprogesterone acetate) and/or Delalutin (17 alpha-hydroxyprogesterone caproate). Serum was examined serially for progesterone (P) and estradiol (E) by radioimmunoassay. Serum from 174 untreated patients with no known complications ranging from 6--40 weeks gestation provided normal distribution data. Of 14 progestagen-treated patients, four aborted during the second trimester. These all had chronically low (greater than 50% of observations were less than 1 standard deviation of the normal population) or falling P/E ratios. The rest delivered normal full-term infants although five of the 10 had chronically low P, seven had chronically low P/E ratios, and in one other P/E was falling. Chronically high E contributed to the low P/E ratio in three cases. Thus, these selected cases with poor obstetrical histories demonstrated steroid patterns outside the +/- 1 standard deviation range, although the steroid levels were still within the normal range. Serum progesterone and estradiol analysis may eventually be useful in identifying patients who will best respond to progestagen treatment.
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PMID:Serum progesterone and estradiol in pregnant women selected for progestagen treatment. 4 Sep 14

The effect of monthly injectios of 300 mg Depo-Provera or 150 mg Deladroxone, and of daily oral administration of .5 mg chlormadinone acetate or .3 mg quingestanol acetate on lactation was studied in Egyptian women during the 1st year of lactation. Women receiving Depo-Provera had the highest milk yield, followed by those taking Deladroxone and quingestanol acetate. The milk yields while taking these hormonal preparations were higher than in untreated controls. However, those women taking chlormadinone acetate had lower milk yields than untreated controls. The increased milk yield is probably due to the progestagenic activity, and minimal estrogenicity, of these drugs.
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PMID:Effect of some progestational steroids on lactation in Egyptian women. I. Milk yield during the first year of lactation. 6 Mar 40

The effect of androgen and different progestins on spermatogenesis was studied in young men with subfertility, prostatovesiculitis and haematospermia, and in older men with benign hypertrophy of the prostate. The compounds (testosterone, testosterone oenanthate, ethinyl oestradiol, megestrol acetate, ethinyl norgestrienone and Depo-Provera) were administered intramuscularly, orally or as subcutaneous silastic implants.
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PMID:Steroidal compounds (injectable and implants) affecting spermatogenesis in men. 6 50

R-2323 and MPA have proved to be potent inhibitors of ovarian function in the female and of spermatogenesis and accessory gland function in the male. This study was to establish methods of determining their concentrations in human plasma in order to obtain more information about their action. Subjects were 10 31-72 year old male patients, who were treated with R-2323 with different dose schedules and 3 men suffering from benign prostatic hypertrophy who were treated with MPA. Plasma levels of testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH), were monitored before, during, and after treatment. R-2323 levels were determined according to the methods of Vunikke et al. Plasma T measurements were done according to the methods of Bartke, LH and FSH levels were measured by means of the modified solid-phase radioimmunoassay method of Crosignani, and MPA determinations were done by the method of Edgvist and Johansson. Individual R-2323 values varied from 16 to 36 ng/ml. After injections of 250-1000 mg of MPA there was less difference in plasma MPA than expected. This suggested that MPA is stored, perhaps in fat tissues. With MPA, a decrease in plasma T levels took place, indicating inhibition of Leydig cell function, within 2-6 days after starting treatment. Treatment with 100 mg of R-2323 weekly for 6 weeks caused a drastic decrease in plasma T levels. Similar changes were found for LH and FSH. The only change in patients' libido was a decrease in the first 2 or 3 weeks of therapy. 6 weeks after treatment was stopped hormone levels had returned to normal in 80% of subjects.
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PMID:Radioimmunoassays of ethinyl-norgestrienone (R-2323) and medroxyprogesterone acetate (MPA) and their clinical applicability. 6 51

6 synthetic steroids were tested subcutaneously in immature female rats for their ability to produce short- and long-term progestational effects. The bioassay of progestational activity which was used has been described by the authors previously. The DR (decidual reaction) was scored macroscopically and microscopically. The results are illustrated with photographs and tabulated. A daily subcutaneous dose of .25 mg of progesterone, administered as a control to certain of the test groups, regularly produced a marked and prolonged effect. Medroxyprogesterone acetate was found to be 5 times more effective than an equal weight of progesterone. Chlormadinone acetate was about as active and Duphaston was slightly less active than progesterone. Depo-Prolutin was tested only for prolonged progestational activity and was without any deciduomagenic effect at these high dose levels. There were no significant differences in body weight gains of the rats in the various experimental groups. The vaginae of all experimental animals with a positive decidual reaction showed a typical mucification of the epithelial cell layer. The ovaries of all the animals who reacted with a distinct decidual reaction showed histologically no presence of corpora lutea.
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PMID:Further studies on a new bioassay of progestational activity (traumatic deciduoma formation in immature rats). 7 88

MAP was used in high doses (1 g/die up to a total dose of 45-50 g) in 44 cases of advanced mammary carcinoma (IIIrd and IVth stage of the T.N.M. classification), evaluated according to the criteria proposed by CBCG. The excellent tolerance to the drug, even at such high doses, is stressed. Therapeutic responses were best in cases of metastasis in the soft and bony tissues and in cases of pulmonary metastasis. It is pointed out that the effectiveness of the treatment is particularly evident in patients in whom the free interval has exceeded two years and in patients in the menopause for more than five years. In the light of results obtained, the possibility of introducing the drug into the therapeutic strategy of this condition is discussed.
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PMID:[Use of high doses of medroxyprogesterone acetate in the palliative treatment of advanced breast cancer. Clinical experience with 44 cases]. 7 11

The "effective" contribution of angiotensin II in blood pressure regulation was investigated in 6 patients on maintenance hemodialysis who were hypertensive at the time of the study (MAP 133 +/- 5 mmHg). Saralasin, a specific angiotensin II inhibitor, was infused at 0.5 and 2.5 microgram/kg/mn three hours before andone hour after hemodialysis. Before hemodialysis, a mean arterial pressure decrease of 13.2 to 19 p. 100 was obtained in 5 patients, arterial pressure being normalized in three of them. After hemodialysis, saralasin induced a normalization of arterial pressure in these 5 subjects. One patient, who was resistant to the saralasin infusion before and after the hemodialysis procedure, can be considered as purely volume-dependent. The renin-angiotensin system is probably one of the primary determinant of dialysis-resistant hypertension. However, a negative response to saralasin should encourage to control hypertension by more vigorous ultrafiltration during dialysis.
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PMID:[Arterial hypertension and maintenance hemodialysis: effects of specific inhibition of angiotensin II by saralasin acetate]. 10 Nov 76


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