Biomedical subjects

E Etemadzadeh

Publications and source records attributed to E Etemadzadeh.

7 recordsLinked to original sources

PubMed1995

Troponin C-mediated calcium sensitization induced by levosimendan does not impair relaxation.

Levosimendan is a novel positive inotropic drug targeted to increase contraction force of the heart through its calcium-dependent binding to troponin C (cTnC). We investigated the calcium-sensitizing effect of levosimendan on contractile proteins as well as its positive inotropic and lusitropic effects in paced guinea pig papillary muscle. We also studied the effect on energy consumption of myosin-actin crossbridges in a myosin ATPase assay. The calcium sensitization induced by levosimendan in fibers skinned with saponin was dependent on the perforation velocity of cell membranes. Levosimendan was almost ineffective in slowly perforated fibers, but was the most potent calcium sensitizer in fibers with rapidly perforated cells. The perforation-dependent calcium sensitization was probably due to changes in phosphorylation state of contractile proteins during the slow dissection of fibers. It is noteworthy that the calcium-sensitizing effect of levosimendan was not affected by acidic pH. Levosimendan at therapeutically relevant (0.3-10 microM) concentrations markedly increased calcium sensitivity both at pH 6.7 and 7.0, being more potent than EMD 53998, pimobendan, and MCI-154. The lack of effect of levosimendan on maximum tension supports the hypothesis that levosimendan increases calcium sensitivity through its action on cTnC. Unlike EMD 53998, levosimendan did not increase myosin ATPase activity, indicating that it did not increase the cycling rate of myosinactin crossbridges. In paced papillary muscles, levosimendan induced positive inotropic effect without changing relaxation time. Thus, levosimendan was devoid of the main negative factors described for calcium sensitizers.

Adenosine Triphosphatases↗

PubMed1994

Cerebral dopamine and noradrenaline in mice withdrawn from repeated morphine treatment and development of tolerance to a test dose of morphine.

1. In mice withdrawn from 3 days of morphine, dopamine depletion was significantly (P < 0.01) retarded in the "rest of the forebrain and midbrain" and tended to be retarded in the striatum. 2. In control mice withdrawn from 3 days of saline treatment a 10 mg/kg test dose of morphine significantly enhanced noradrenaline depletion in all selected brain areas. This did not occur in test mice withdrawn from 1-3 days of morphine, indicating development of tolerance. 3. These results suggest that dopamine depletion is retarded in the "rest of the forebrain and midbrain" of mice withdrawn from 3 days of repeated morphine and that noradrenaline depletion is unchanged in all selected brain areas of mice withdrawn from morphine. 4. Tolerance develops to the enhancing effect of morphine on noradrenaline depletion in mice withdrawn from 3 days of repeated morphine but not in those withdrawn from 1 day of treatment only.

Animals↗

PubMed1993

Cerebral catecholamine depletion in mice withdrawn from repeated morphine treatment and development of tolerance to the enhancing effect of morphine on noradrenaline depletion.

The effect of repeated morphine administration on the alpha-methyl-rho-tyrosine (alpha M rho T)-induced depletion of catecholamines was investigated in various brain areas of mice withdrawn for 1, 2, 3 and 7 days from 5-day morphine treatment. In addition, to clarify the development of tolerance, the effect of acute morphine administration on alpha M rho T-induced depletion of catecholamines was studied in these selected brain areas of mice withdrawn from repeated morphine treatment. Dopamine depletion was significantly (P < .01) retarded in the striatum and "rest of forebrain + midbrain" of mice withdrawn for 1 day from morphine treatment. Withdrawal from morphine treatment did not alter alpha M rho T-induced noradrenaline depletion in the lower brain stem, rest of forebrain + midbrain or hypothalamus. The 10-mg/kg test dose of morphine significantly enhanced alpha M rho T-induced dopamine depletion in the rest of forebrain + midbrain of control mice withdrawn for 2 days, but did not clearly enhance it in mice withdrawn from morphine. The test dose significantly enhanced noradrenaline depletion in all selected brain areas of control mice withdrawn for 1 to 3 days from saline, but tolerance to the test dose developed in morphine-withdrawn mice. These results suggest that dopamine depletion is retarded in the striatum and rest of forebrain + midbrain of mice withdrawn for 1 day from repeated morphine treatment. However, noradrenaline depletion remains unchanged in all selected brain areas of mice withdrawn from morphine, and tolerance develops to the enhancing effect of morphine on the depletion of noradrenaline in mice withdrawn for 1 to 2 days from morphine.

Animals↗

PubMed1989

Computerized rotometer apparatus for recording circling behavior.

A computerized rotometer for recording rotational behavior in rats is described. The digital pulses derived from the infrared photocell detector induced by animal rotations were input directly to a 20-megabyte microcomputer for on-line recording and were processed further to the Digital Equipment Corporation's VAX computer with the SAS software system for statistical and graphical analysis. The typical results obtained with drugs (apomorphine and amphetamine) eliciting contralateral and ipsilateral rotation in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal dopamine pathway were presented. The effect of catechol-O-methyltransferase (COMT) inhibitor, OR-611, on the potentiation of L-dopa-induced contralateral rotation in 6-OHDA-lesioned rats was also studied. The automation of rotometer apparatus and the speed of data analysis facilitate screening novel antiparkinsonian drugs in rats with unilateral lesions of 6-OHDA.

Animals↗

PubMed1988

Favorable effect of catechol-O-methyltransferase inhibition by OR-462 in experimental models of Parkinson's disease.

A selective catechol-O-methyltransferase inhibitor, OR-462, was studied for its ability to affect pharmacokinetic properties of L-dopa after the p.o. administration of the inhibitor to rats and mice. When OR-462 was given to rats at the dose range of 0.3 to 30 mg/kg in conjunction with L-dopa and carbidopa, a dose-related and long-lasting (greater than 5 hr) increase in striatal L-dopa and dopamine levels as well as a reduction in 3-O-methyldopa levels were shown. For a 50% reduction of the 3-O-methyldopa levels a dose of 6 mg/kg of OR-462 was needed. The increase in striatal homovanillic acid, an O-methylated metabolite of dopamine which poorly penetrates the blood brain barrier, indicates that O-methylation was not inhibited in the brain. In order to get the same dopamine levels in striatum the L-dopa dose could be lowered to one-fourth when OR-462 was added. The L-dopa-sparing effect of OR-462 given p.o. was also demonstrated in two behavioral parkinsonian models. OR-462 given at doses of 3 to 30 mg/kg in conjunction with L-dopa and carbidopa, dose-dependently potentiated the L-dopa-induced reversal of hypoactivity in reserpinized mice. Likewise, the same doses of OR-462 caused a marked potentiation of L-dopa-induced contralateral turning behavior in rats with unilateral nigrostriatal lesions produced by 6-hydroxydopamine. The data suggest a possible beneficial effect of OR-462 in the therapy of Parkinson's disease.

Animals↗

PubMed1988

Comparative studies on the dependence liability of morphine hydrochloride, codeine phosphate and two novel antitussive compounds vadocaine hydrochloride and N-(2',4'-dimethyl-6'-methoxyphenyl)-4-(diethylamine) butanamide hydrochloride in mice.

The effects of two novel antitussive compounds, vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) and N-(2,4-dimethyl-6-methoxyphenyl)-4-(diethylamine)butanamide hydrochloride (OR K-269-HCl) on the suppression of withdrawal signs (hypothermia and weight loss) induced by repeated morphine administration were compared to those of acute morphine and codeine administrations. Moreover, spontaneous and precipitated withdrawal-induced hypothermia, weight loss and behavioural changes from repeated codeine, vadocaine and OR K-269-HCl administrations were studied. Acute administration of morphine clearly reversed the hypothermia and weight loss induced by spontaneous withdrawal from morphine. Codeine was not able to suppress the hypothermia and weight loss induced by morphine withdrawal. Acute injections of vadocaine and OR K-269-HCl did not alter these withdrawal signs either. Moreover, acute administration of codeine tended to prevent the weight loss induced by codeine withdrawal and caused behavioural changes. Spontaneous or precipitated withdrawal from repeated vadocaine or OR K-269-HCl administration caused neither hypothermia, weight loss nor behavioural changes. These results support the view that compounds vadocaine and OR K-269-HCl are free from morphine-like addictive properties.

Animals↗

PubMed1987

Differences in the effects of morphine on the alpha-methyl-p-tyrosine-induced depletion of dopamine and noradrenaline in various areas of the mouse brain.

The effect of morphine on the alpha-methyl-p-tyrosine (alpha MT)-induced depletion of dopamine (DA) and noradrenaline (NA) was studied in various brain areas of male NMRI mice, whose locomotor activity is clearly stimulated by morphine. Morphine (10 mg/kg) accelerated the alpha MT-induced DA depletion in the striatum and in the area "rest of forebrain + midbrain", which contains the limbic dopaminergic neurons, but did not clearly alter it in the hypothalamus. The effects were blocked by naloxone. The enhancement of the striatal DA depletion was attenuated when morphine was given after alpha MT or when morphine dose was increased to 30 mg/kg. The smallest dose of morphine to enhance the alpha MT-induced NA depletion in the forebrain + midbrain area was 3 mg/kg, and in the hypothalamus and the lower brain stem 10 mg/kg. The enhancement of the NA depletion was dose-dependent, occurred whether morphine was given before or after alpha MT, and was blocked by naloxone. Our findings suggest that morphine alters the alpha MT-induced depletion of cerebral DA in mice similarly to what has been reported to occur in rats. In contrast its effects on cerebral NA depletion in mice are clearly different from its effects in rats. The substantial activation of cerebral noradrenergic systems, especially of those in the forebrain + midbrain area, in mice could underly the fact that morphine's predominant behavioural effect in mice is stimulation of motor activity.

Animals↗