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C Nath

Publications and source records attributed to C Nath.

At least 37 records · Page 2Linked to original sources
PubMed1995

Novel met-enkephalin analogue: a potent systemic mu agonist antinociceptive agent.

A new met-enkephalin analogue (compound 82/205) was evaluated for its opioidergic activity in mice. The compound showed antinociception (warm water tail-flick test), tolerance, cross tolerance to morphine and physical dependence. The time course of antinociceptive effect of the compound was comparable to morphine. The antinociceptive ED50 (mumol kg-1, i.p.) values for the compound and morphine base were 5.31 and 7.59, respectively. Its antinociceptive effect was blocked by naloxone, beta-FNA (mu antagonist) and naloxonazine (mu1 antagonist) but not by ICI 174,864 (delta antagonist). Naloxone precipitated withdrawal jumpings were 2.6 times less in compound 82/205 treated mice than the morphine treated group. The new analogue compound 82/205 is a potent mu agonist antinociceptive with a possible weak dependence liability.

Analgesics↗
PubMed1994

Morphine-induced straub tail response: mediated by central mu2-opioid receptor.

The opioid receptor mechanism involved in the morphine induced straub tail response was investigated in mice. Morphine (2.5, 5, 10 and 20 mg/kg s.c.) produced a dose dependent straub tail response and analgesia (hot plate test). Naloxone (5 mg/kg s.c.) and the mu-opioid receptor antagonist beta-funaltrexamine (10 micrograms i.c.v.) blocked both the straub tail response and analgesia while the mu 1-opioid receptor selective antagonist naloxonazine (35 mg/kg s.c.) blocked only analgesia and did not affect the straub tail response. Morphine (20 micrograms) administered by the i.c.v. route also produced the straub tail response as well as analgesia. Pretreatment with naloxonazine (35 mg/kg s.c.) antagonised i.c.v. administered morphine induced analgesia while the straub tail response was not affected. The results indicate that the morphine induced straub analgesia while the straub tail response was not affected. The results indicate that the morphine induced straub tail response is mediated by central mu 2-opioid receptors.

Analgesia↗
PubMed1993

Suppression of phase separation in bovine gamma IV crystallin solutions: effect of modification by charged versus uncharged polar groups.

gamma IVa Crystallin, the ocular lens protein with the highest critical temperature (Tc) for phase separation, has been chemically modified with N-ethylmaleimide (NEM) at neutral pH. NEM, a polar but uncharged modifier reacts with the cysteine residues of the protein. A maximum of 80-85% of the thiol groups are modified and the phase separation temperature is lowered by about 10 degrees C at a protein concentration of 30 mg ml-1. The coexistence curve of the NEM-modified protein with nearly four out of the six cysteines modified was determined and compared with that obtained by modifying the protein with a charged reagent, N-bromoacetylethanolamine phosphate (NBAEP). NBAEP modifies both cysteine and methionine residues of gamma IVa crystallin. The results of these two modification studies indicate that for the same total degree of modification of the sulfur-containing residues, the suppression in Tc due to the charged NBAEP is at least twice as large as that due to the polar but uncharged NEM. In order to obtain some measure of the relative hydrophilicities of the two modifiers, we have estimated the free energies of hydration of the nonionic segments of NEM and NBAEP, using structural additivity schemes. We find that the intrinsic hydrophilicities of the nonionic segments of these two modifiers are nearly equal. Hence the much larger suppression of Tc resulting from NBAEP modification is most probably due to the strongly polar, doubly charged phosphate group.

Amino Acids↗
PubMed1993

Dopaminergic involvement in the effects of piracetam on foot shock induced aggression in mice.

The effects of piracetam-a nootropic drug, were studied on foot shock induced aggressive behaviour in mice. Intraperitoneal injection of piracetam resulted in a biphasic response i.e.; initial excitation followed by inhibition of the aggressive behaviour. The initial excitation was observed with only 100 and 50 mg/kg doses of piracetam and not with the lower doses (25 and 12.5 mg/kg). Dopaminergic receptor blocker haloperidol (0.5; 0.25 and 0.12 mg/kg, ip) and pimozide (1.0 mg/kg, ip) produced inhibition of the aggressive behaviour. Lowering of the dose of haloperidol to 0.06 mg/kg resulted in an excitation of the aggressive behaviour. No motor deficit or catalepsy was observed with either haloperidol or pimozide injected in the doses indicated above. Pretreatment of the mice with haloperidol (0.12; 0.25 and 0.5 mg/kg) led to a dose-dependent blockade of the piracetam (100 mg) induced excitation of the aggressive behaviour, but the inhibition of the aggressive behaviour was not blocked by pretreatment with the excitatory dose of haloperidol. Similarly, pimozide (1.0 mg/kg) pretreatment also effectively blocked the excitatory effect of piracetam on aggressive behaviour. The results suggest the involvement of dopaminergic system in the excitatory effects of piracetam on aggressive behaviour. The inhibitory effect of piracetam appears to be independent of this mechanism.

Aggression↗
PubMed1991

Protection against gastric ulcer by verapamil.

The effect of verapamil, a calcium channel blocker, was studied against stress (cold restraint), aspirin and pylorus ligation induced gastric ulcers in rats. Verapamil inhibited ulcerogenic response and ulcer index in all the three types of ulcers. Verapamil also decreased total and free gastric acidity without changing gastric secretory volume.

Animals↗
PubMed1991

Novel effects of MPTP: MAO-B unrelated opioidergic activity in mice.

The presence of opioidergic activity after i.p. injection of N-methyl-4-phenyl tetrahydropyridine (MPTP) has been investigated in albino mice by studying analgesia and the Straub reaction. MPTP (6.25-25 mg kg-1) produced a dose-related analgesic response and Straub reaction. These effects of MPTP were effectively antagonized by prior naloxone treatment but remained unaffected after the MAO-B inhibitor deprenyl. MPTP thus possesses significant opioidergic activity and this, unlike its neurotoxic actions, does not appear to be dependent on oxidative conversion to MPP+ (1-methyl-4-phenyl pyridinium).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Cardiovascular adaptations in Andean natives after 6 wk of exposure to sea level.

Six male Quechua Indians (34.0 +/- 1.1 yr, 159.5 +/- 2.1 cm, 60.5 +/- 1.6 kg), life-long residents of La Raya, Peru (4,350-m altitude with an average barometric pressure of 460 Torr), were studied using noninvasive methods to determine the structural and functional changes in the cardiovascular system in response to a 6-wk deacclimation period at sea level. Cardiac output, stroke volume, and left ventricular ejection fractions were determined using radionuclide angiographic techniques at rest and during exercise on a cycle ergometer at 40, 60, and 90% of a previously determined maximal O2 consumption. Subjects at rest were subjected to two-dimensional and M-mode echocardiograms and a standard 12-lead electrocardiogram. Hemoglobin and hematocrit were measured on arrival at sea level by use of a Coulter Stacker S+ analyzer. After a 6-wk deacclimation period, all variables were remeasured using the identical methodology. Hemoglobin values decreased significantly over the deacclimation period (15.7 +/- 1.1 to 13.5 +/- 1.2 g/dl; P less than 0.01). The results indicate that the removal of these high-altitude-adapted natives from 4,300 m to sea level for 6 wk results in only minor changes to the cardiac structure and function as measured by these noninvasive techniques.

Acclimatization↗
PubMed1989

Improved anticonvulsant activity of phenytoin by a redox brain delivery system. III: Brain uptake and pharmacological effects.

Phenytoin (DPH) was delivered to the brain by a dihydropyridine in equilibrium pyridinium salt redox system, which was evaluated for anticonvulsant activity. Following iv injection of the lipophilic delivery system of DPH (2) to rats, concentrations of DPH were lower but sustained and, after 30 min, essentially the same as the levels after equimolar administration of DPH. While 2 delivered the same levels of DPH to the brain as DPH did, it was twice as potent as DPH in rats (ED50 was 7.5 mumol/kg for 2 and 14.2 mumol/kg for DPH) and mice (2: 10.5; DPH: 23.9) against maximal electroshock seizures (MES), and seven times more potent in mice (2: 10.0, DPH: 70.6) against maximal pentylenetetrazole seizures (MPS). Moreover, 2 was active against pentylenetetrazole threshold seizures (PTS) in mice and rats (ED50 = 44.1 and 40.5 mumol/kg, respectively), while DPH was ineffective (up to a dose of 79.2 mumol/kg). After evaluation of acute neurological toxicity in rats, 2 was found to possess 1.5 times higher a protective index (for MES) than DPH. It appeared also that while DPH was 2.9 times less sensitive to MPS than to MES, 2 was equally potent to both types of convulsions. Thus, the data indicate that 2 delivered DPH more efficiently to the brain. The better anticonvulsant activity (quantitatively as well as qualitatively) of 2 can be explained on the basis of an improved distribution in the brain due to its higher lipophilicity, and by favorable regional differences in the rates of conversion of 2 to DPH at the convulsing foci.

Animals↗
PubMed1988

Role of central histaminergic mechanism in behavioural depression (swimming despair) in mice.

The role of the central histaminergic system in depression was studied by using swimming despair test in mice - a behavioural model of depression. In this test, immobility of mice reflects a state of depression. Intracerebral (ic) injection of histamine (50-200 micrograms) increased significantly the immobility. The H1-receptor blocker mepyramine (2.5-20 mg/kg ip) had no effect while H2-receptor blocker cimetidine (100-200 micrograms ic) caused a significant decrease in immobility. The histamine induced facilitation was blocked completely by cimetidine and antidepressant drugs-imipramine and desipramine, but remained unaffected in mice pretreated with mepyramine or atropine. The H2 agonist impromidine (20-40 micrograms ic) also enhanced significantly, the immobility which was blocked by cimetidine and antidepressant drugs. It has been concluded that central H2-receptors facilitate depression and antidepressant drugs block central H2-receptors.

Animals↗
PubMed1987

The blood pressure responses of thiazide-resistant hypertensives to a once-a-day bevantolol regimen.

The antihypertensive efficacy of a single daily dose of bevantolol (200 mg) alone or in combination with hydrochlorothiazide (25 mg) has been compared against conventional twice daily propranolol (80 mg) therapy in a group of 22 hypertensive patients whose blood pressures did not respond to thiazide monotherapy. Addition of bevantolol to the diuretic resulted in a significant (P less than 0.001) fall in sitting blood pressures (144/97 to 137/90 mmHg), supine blood pressures (147/100 to 141/92 mmHg) and heart rate (83 to 73 beats/min) 24 h after administration. When the diuretic was withdrawn, heart rate and diastolic pressures remained unchanged and within normotensive limits but systolic pressures increased to pre-treatment levels. Substitution of propranolol for bevantolol gave results comparable to the combined bevantolol-diuretic regimen except that heart rate was still lower (66 beats/min). No significant adverse reactions were reported. In thiazide-resistant hypertensives, a once daily dose of 200 mg bevantolol effectively reduced diastolic blood pressures towards normotensive limits and to an extent comparable with twice daily propranolol therapy.

Adrenergic beta-Antagonists↗
PubMed1987

Hemodynamic and neurohumoral factors in the response of hypertensives to hydrochlorothiazide therapy.

We investigated the roles of the renin-angiotensin-aldosterone axis, the sympathetic nervous system, and the responses of the forearm vascular bed in the antihypertensive action of hydrochlorothiazide. Plasma renin activity, aldosterone, catecholamines, blood pressure, and forearm blood flow were measured before and after 8 weeks of hydrochlorothiazide therapy in 21 hypertensive patients whose blood pressures responded to the diuretic, and were then compared to a similar group of 19 hypertensives who did not respond to the thiazide therapy. Dietary salt intake was stable and comparable for the two groups. In the responsive patients, administration of the diuretic caused a significant fall in supine systolic and diastolic blood pressure and forearm vascular resistance, with constant forearm blood flow. No significant changes were noted in these parameters in the non-responsive group. Plasma renin activity and aldosterone concentration was increased in both groups to a comparable extent but plasma norepinephrine and epinephrine concentrations were increased to a greater extent (p less than 0.01) in the responsive group. Heart rate did not change significantly in either group in spite of significant increases in circulating epinephrine. The results are consistent with minimal thiazide-induced volume and salt depletion in either study group. The reduction in blood pressure and forearm vascular resistance observed in the responsive group appears to be the result of diminished target-organ sensitivity towards catecholamines and possibly angiotensin II.

Aldosterone↗
PubMed1986

Increased metabolic heat production following chronic alpha-methyldopa therapy in hypertensives.

The objective of this study was to measure metabolic heat production in mild-moderate hypertensives when given chronic alpha-methyldopa for control of hypertension and to compare this with hydrochlorothiazide. Four men and one woman, age range 29-55 years, euthyroid, and not previously on alpha-methyldopa, had their drugs replaced by placebo for 4 weeks, and then alpha-methyldopa or hydrochlorothiazide was randomized single blindly to patients. The dose of each drug was increased until the ambulatory diastolic blood pressure was less than 95 mmHg (1 mmHg = 133.322 Pa), and then the dose was maintained for 20-24 weeks. The two active drugs were then crossed over, and each medication was again titrated to attain diastolic normotension (less than 95 mmHg). Maintenance was for a comparable 20-24 weeks. At week 4 (end of placebo period), weeks 20-24 (for hydrochlorothiazide or alpha-methyldopa monotherapy), and again at week 40-48 (end of cross-over period), metabolic heat production (watts), heart rate (beats per minute), and blood pressure (millimetres of Hg) were measured in a resting sitting position for 1 h in a whole body calorimeter (air temperature 28 degrees C and a dew point temperature less than 5 degrees C) for 15 experimental sessions. In four out of five patients, metabolic heat production was significantly (P less than 0.05) higher when patients were treated with alpha-methyldopa. We speculate from our data that alpha-methylnorepinephrine, the major metabolite of alpha-methyldopa, may be thermogenic and that this should be considered when the drug is prescribed.

Aged↗
PubMed1986

High performance liquid chromatography analysis of nifedipine and some of its metabolites in hypertensive patients.

Techniques are described for the analysis of nifedipine and three of its metabolites; dehydronifedipine (I), dehydronifedipinic acid (II), and dehydronifedipinolactone (III) in human serum and urine. The analytes are extracted at pH 9 or 3 with ethyl acetate and chromatographed on a C8 reverse-phase column. Recoveries from spiked control serum and urine ranged from 70 to 95% depending on the polarity of the analyte. The coefficient of variation ranged from 10 to 15% (nifedipine, I, and III at 50-200 ng/mL) and 15-20% (II at 200-2000 ng/mL). Accuracy was always within the limits of precision. The metabolism of nifedipine in a group of hypertensive patients receiving long-term nifedipine therapy was compared with that reported for acute administration. Serum nifedipine levels were comparable in both cases, but contrary to previous reports, dehydronifedipine was consistently found in significant amounts. Serum levels of II were considerably elevated but III was not detected either in serum or in urine. Thus, prolonged nifedipine therapy in conjunction with other antihypertensive medications appears to be associated with significant alterations in the metabolism of nifedipine compared with acute administration.

Aged↗
PubMed1986

The metabolism of nifedipine during long-term therapy.

The serum concentrations and urinary excretion of nifedipine and 3 of its metabolites have been compared in two groups of hypertensive patients, one receiving prolonged (1-2 years) nifedipine monotherapy, the second receiving the same dosage of nifedipine in conjunction with a variety of other antihypertensive and cardioactive drugs. It was found that prolonged administration of nifedipine was associated with an eight-fold reduction in serum nifedipine concentration, one hour following a 10 mg dose, compared with the levels observed at the same time after an acute 10 mg dose. The serum concentration of the metabolite dehydronifedipinic acid was concomitantly increased, but no evidence for dehydronifedipinolactone, derived from hydroxylation of dehydronifedipinic acid, was found. When the nifedipine was administered as part of polytherapy, there was a marked (p less than 0.001) increase in the serum concentration of the drug as compared with monotherapy, together with a significant (p less than 0.05) increase in the serum concentration of its metabolites. The results suggest that while a significant enhancement of nifedipine metabolism occurs during long-term monotherapy, chronic administration of nifedipine as part of polytherapy appears to be associated with significant inhibition of the initial oxidation of nifedipine to dehydronifedipine, which may be attributable to the actions of the co-administered drugs. The subsequent hydrolysis of dehydronifedipine to dehydronifedipinic acid and the excretion of the latter metabolite appear to be much less affected, but subsequent oxidation of dehydronifedipinic acid may also be inhibited.

Chemical Phenomena↗
PubMed1985

Effect of alcohols on the permeability of blood-brain barrier.

Effect of alcohols on the permeability of blood-brain barrier was studied in anaesthetised dogs using sodium fluorescein as circulant. Entry of sodium fluorescein in the cerebrospinal fluid (CSF) was measured spectrophotofluorometrically. Methyl, ethyl, propyl and butyl alcohols were used in the study. Methyl alcohol did not increase the entry of sodium fluorescein in CSF compared to control. However, ethyl, propyl and butyl alcohols significantly increased the entry of sodium fluorescein. The increase was dependent upon the length of alkyl chain of alcohols. Longer was the aliphatic chain more marked was the effect. The increase in permeability was also dependent upon the concentration of the alcohol. Thus 90% ethyl alcohol was more effective than 30% and this effect was concentration-dependent. The increase in permeability of blood-brain barrier could be correlated to the lipid solubility of alcohols.

1-Propanol↗