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Biomedical subjects

Y Kumar

Publications and source records attributed to Y Kumar.

At least 37 records · Page 2Linked to original sources
PubMed1990

Potential antipsychotic agents. 7. Synthesis and antidopaminergic properties of the atypical highly potent (S)-5-bromo-2,3-dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide and related compounds. A comparative study.

(S)-5-Bromo-2,3-dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide (6) and some related compounds, i.e. the R isomer 7, the 3-hydroxy analogue 8, the desbromo derivative 9, the monomethoxy compound 10, and the 2,4-dimethoxy analogue 11, have been synthesized from the corresponding benzoic acids. The benzamides, lacking o-hydroxy groups, were evaluated for their affinity for the [3H]spiperone binding site and for their inhibition of apomorphine-induced behavioral responses in relation to the effect of the corresponding salicylamides. Besides the 2-hydroxy-3-methoxybenzamide 12 and the related 1,4-benzodioxane (13) and 2,3-dihydrobenzofuran (14), carboxamides were investigated in order to evaluate the stereoelectronic requirements on the 2-methoxy group for the receptor interaction. The study supports the view that the o-methoxy group may adopt coplanar, as well as perpendicular orientations, and maintain the intramolecular hydrogen bonding required in the bioactive conformation. The benzamide 6 was found to be equipotent with the analogous highly active salicylamide 3 (FLB 463) both in vitro and in vivo. In addition, 6 displayed a preferential inhibition of the hyperactivity component of the behavioral syndrome, which is regarded to indicate a low tendency to induce extrapyramidal side effects in man at antipsychotically effective doses. The benzamide class of compounds (6-10) were found to be somewhat more sensitive to the structural modifications than the salicylamide class, i.e. the o-hydroxy-substituted benzamides (2-5). The potent and selective benzamide 6 (FLB 457) is highly suitable for investigations of dopamine D-2 mediated responses and, in radiolabeled form, for receptor binding studies in vitro and in vivo.

Animals↗
PubMed1989

Arterial to end-tidal carbon dioxide tension difference during anaesthesia in early pregnancy.

Sixteen patients requiring general anaesthesia for termination of pregnancy by dilatation and evacuation of the uterus were studied. Arterial and end-tidal carbon dioxide tensions were determined during anaesthesia. The mean arterial to end-tidal carbon dioxide tension difference was 0.07 kPa (-0.02-0.16, 5-95 per cent confidence limits). These results were similar to those observed during Caesarean section and those during anaesthesia for post-delivery tubal ligations. The physiological changes such as increased cardiac output, haemodilution, and increased blood volume which manifest by 12 weeks of gestation probably result in a reduced (a-E')PCO2 value.

Abortion, Induced↗
PubMed1988

Effect of alcohol on glucose tolerance in normal and noninsulin-dependent diabetic subjects.

Oral glucose tolerance tests were conducted in 10 noninsulin-dependent diabetic and 14 healthy control subjects with a 75-g glucose load. The tests were repeated 1 week later with 43 g of ethanol mixed with the glucose. Blood samples were analyzed for ethanol, glucose, insulin, C-peptide, and glucagon levels. The blood ethanol peak was nearly equal in diabetic and control subjects (mean +/- SEM values of 55 +/- 8 and 48 +/- 6 mg/dl 45 min after ethanol ingestion). Ethanol did not affect glucose tolerance in either of the study groups. Mean +/- SEM values of the sum of the increment above the baseline glucose level were 659 +/- 48 vs. 675 +/- 76 mg/dl with or without ethanol in diabetics and 227 +/- 35 vs. 244 +/- 36 mg/dl in control subjects. The plasma insulin and C-peptide responses to glucose were delayed in diabetic patients compared to controls but were not affected by ethanol. In vitro, ethanol, at a concentration of 100 mg/dl or greater, significantly decreased insulin binding to erythrocytes in a dose-related manner. Scatchard analysis of competitive insulin binding to erythrocytes indicated that ethanol reduced insulin binding affinity (1.6 +/- 0.5 vs. 4.2 +/- 0.8 x 10(8)/M), but not binding capacity (4.5 +/- 2.4 vs. 4.4 +/- 1.7 nM, with and without ethanol, respectively).

Alcohol Drinking↗
PubMed1987

Physiological dead space during general anaesthesia for Caesarean section.

The physiological dead space and its components were determined during general anaesthesia for Caesarean section in seventeen patients and compared with similar values for seventeen patients undergoing abdominal hysterectomy under general anaesthesia. The physiological dead space was smaller in the pregnant patients, due to a smaller alveolar dead space. The anatomical dead space was similar in both groups. A lowered physiological dead space suggests that there will be a decrease in the pulmonary ventilation perfusion ratio (V/Q) during Caesarean section; this could result from better perfusion of the ventilated alveoli than in the non-pregnant group, due to the increased cardiac output of pregnancy. An improvement in alveolar perfusion should also produce more efficient carbon dioxide elimination in pregnant patients, when compared to non-pregnant subjects.

Adult↗
PubMed1987

Arterial to end-tidal carbon dioxide tension difference during anaesthesia for tubal ligation.

Twenty-nine patients scheduled for postnatal tubal ligation by minilaparotomy under general anaesthesia were studied. Arterial and end-tidal carbon dioxide tensions were determined during anaesthesia. The mean arterial to end-tidal carbon dioxide tension difference was 0.08 kPa (SEM 0.05). Thirty-one percent of the patients had negative values. These results were similar to those observed during Caesarean section. The physiological changes responsible for reduced arterial to end-tidal carbon dioxide values, persist into the postnatal period. It is predicted from the regression analysis of the time between delivery and anaesthesia for tubal ligation and arterial to end-tidal CO2 difference, that the values might return to normal nonpregnant levels by 8 days following delivery.

Adult↗
PubMed1986

Hypothyroidism with angina pectoris. A clinical dilemma.

Management of patients with chest pain and hypothyroidism is a clinical dilemma. Thyroid replacement therapy may exacerbate angina pectoris. Administration of a beta blocker such as propranolol (Inderal) concomitantly with thyroid replacement therapy is useful in treatment of angina. However, beta blockers can induce variant angina owing to increased norepinephrine secretion and enhanced alpha-mediated responsiveness in the hypothyroid state. Hypotension and syncopal episodes may develop in the hypothyroid patient after administration of nitrates. Cardiac catheterization and revascularization are well tolerated by myxedematous patients with angina. After surgery, full thyroid replacement therapy should be initiated gradually and with caution.

Angina Pectoris↗
PubMed1986

Potential neuroleptic agents. 4. Chemistry, behavioral pharmacology, and inhibition of [3H]spiperone binding of 3,5-disubstituted N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamides.

A series of 3,5-disubstituted N-[(1-ethyl-2-pyrrolidinyl) methyl]-6-methoxysalicylamides was synthesized, starting from the 2,6-dimethoxybenzoic acids, by boron tribromide demethylation of the corresponding 3,5-disubstituted 2,6-dimethoxybenzamides and separation of the two positional isomers. The correct structure assignments were based on selective decoupling studies on their 13C NMR spectra. The salicylamide derivatives were tested for antidopamine activity in vivo by their ability to inhibit the apomorphine syndrome in the rat and in vitro by their ability to displace [3H]spiperone from striatal preparations of the rat brain. The activity seems to reside exclusively in the S enantiomer. Several compounds were considerably more potent than haloperidol, particularly those having an ethyl group in the 3-position and a halogen atom in the 5-position of the aromatic ring. The corresponding 5-alkyl-3-halogen-substituted compounds were much less active. A low acute toxicity was found for the most potent compounds. Some of the salicylamides displayed a 10-20-fold separation between the dose which blocks apomorphine-induced hyperactivity and that which blocks apomorphine-induced stereotypy. One compound, S-(-)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl) methyl]-6-methoxysalicylamide (raclopride, FLA 870) (13) had a stereotypy--hyperactivity separation more than twice that of sulpiride while being 100 times more potent in blocking the apomorphine effects. On this basis, 13 was selected for clinical trials against schizophrenia.

Animals↗
PubMed1986

Selective monoamine oxidase inhibitors. 3. Cyclic compounds related to 4-aminophenethylamine. Preparation and neuron-selective action of some 5-(2-aminoethyl)-2,3-dihydroindoles.

Nine 5-(2-aminoethyl)-2,3-dihydroindole derivatives were synthesized and tested as monoamine oxidase (MAO) inhibitors in vitro and in vivo. All compounds were found to be selective MAO-A inhibitors in vitro, the most active ones, 5-[1-(2-aminopropyl)]-2,3-dihydro-4-methylindole acetate (3), 5-[1-(2-aminopropyl)]-4-chloro-2,3-dihydroindole acetate (5), 5-[1-(2-aminopropyl)]-2,3-dihydro-1-ethyl-4-methylindole tartrate (6), 5-[1-(2-aminopropyl)]-2,3-dihydro-1-ethyl-6-methylindole tartrate (7), and 5-[1-(2-aminobutyl)]-4-chloro-2,3-dihydroindole acetate (9) being equipotent with amiflamine, (S)-(+)-4-(dimethylamino)-2, alpha-dimethylphenethylamine. Some of the compounds, 3, 6, 5-[1-(2-aminopropyl)]-2,3-dihydroindole acetate (1), and 5-[1-(2-amino-2-methylpropyl)]-2,3-dihydroindole acetate (8), were found to be very potent inhibitors of MAO in serotonergic and/or noradrenergic nerve terminals in the rat brain in vivo, inhibiting MAO within these neurons at doses 1/10 of those required to inhibit MAO in other neurons or cells. Compound 1 was also a potent and selective inhibitor of MAO within dopaminergic nerve terminals in vivo. This neuron selectivity is due to the uptake of these compounds by the neuronal uptake mechanisms.

Animals↗
PubMed1986

Arterial to end tidal carbon dioxide tension difference during caesarean section anaesthesia.

The relationship between arterial carbon dioxide tension and end tidal carbon dioxide tension was studied in 19 patients during general anaesthesia for Caesarean section. Thirteen patients scheduled for elective abdominal hysterectomy formed a nonpregnant group. There was significant correlation between arterial and end tidal CO2 tensions in both groups. During Caesarean section, this difference was significantly less than in the nonpregnant group.

Adult↗