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Biomedical subjects

M Mahmoudian

Publications and source records attributed to M Mahmoudian.

At least 19 recordsLinked to original sources
PubMed2006

Effect of sildenafil (Viagra) on memory retention of a passive avoidance response in rats.

The effects of an intraperitoneal (i.p.) injection of different doses of sildenafil, a cyclic guanosin monophosphate (cGMP) specific phosphodiesterase type 5 (PDE 5) inhibitor, on memory retention of young (2-month-old) and middle aged (12-month-old) male Wistar rats were investigated. Passive avoidance behaviour was studied in a one trial learning, step--through type, passive avoidance task utilizing the natural preference of rats for a dark environment. In each category (young or middle-aged) different groups of rats received vehicle or sildenafil (1, 3, 10, 20 mg*kg(-1), i.p.) immediately after training and one group remained uninjected serwing as control. Retention latencies were measured 48 h later. To asses a possible non-specific proactive effect of sildenafil, the response latencies in a group of rats not receiving foot shock were also tested. The results showed that the post-training i.p. administration of sildenafil did not facilitate retention performance of a passive avoidance response in both young and middle aged rats compared to control or vehicle groups. Also, sildenafil did not affect response latencies in rats not having received the footshock on the training trial, indicating that sildenafil does not show a non-specific proactive affect on retention performance. The comparison of retention time between young and middle aged rats showed that the memory of the latter had been significantly reduced. In conclusion, this study suggests that sildenafil has no effects on memory retention in Wistar rats.

Age Factors↗
PubMed2006

Interaction of papaverine with the enalapril-induced cough in guinea pig.

BACKGROUND: Angiotensin Converting Enzyme Inhibitors (ACEIs) like enalapril are extremely effective in the treatment of hypertension and heart failure. One of the most important side-effects of these drugs which can lead to cessation of therapy is a persistant dry cough, induced because of increased bradykinin levels in the lung. Although antitussive alkaloids like codeine are effective in suppressing this cough, they too present a wide range of side-effects, most notably addiction. OBJECTIVE: In a previous work we were able to show that noscapine, a non-narcotic antitussive agent, was able to decrease enalapril induced cough in guinea pigs. In this work, papaverine, another non-narcotic alkaloid found in opium latex was tested in the guinea pig model for antitussive activity. METHOD: Cough was induced in enalapril pretreated guinea pigs by forcing the animals to inspire capsaicin aerosol in an air-tight chamber. Coughs were recorded in control animals and in those which had received different doses of papaverine. Characteristic changes in chamber air pressure, were detected by a pressure transducer. RESULTS: . At low doses (0.5 and 0.25 mg/kg) papaverine was able to decrease enalapril induced cough. CONCLUSION. This effect was not mediated by the action of the drug on mu receptors and was only observed in animals treated with enalapril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Solid-phase microextraction (SPME) of permethrin residues from cucumber using a silica-bonded phase-coated stainless steel fibre.

Solid-phase microextraction (SPME) is a rapid, economic and solvent-free sample preparation method for the isolation of an analyte from its matrix. The technique uses a few centimetres of some adsorptive materials such as activated charcoal, polydimethylsiloxane or octadecyl silane coated onto fused silica optical fibres or, more recently, stainless steel fibres mounted into a microsyringe. The proposed method allows the extraction of permethrin from cucumber matrix into the coating, avoiding sample handling and saving evaporation of solvents and concentration steps. Adsorbed permethrin was desorbed in the split/splitless injection port of the gas chromatograph. The time required for each run was about 1.5 h, which gave a preconcentration of several orders of magnitude. The method could separate and quantify cis- and trans-isomers of permethrin. The calibration curve showed linearity in the range 1-9 micrograms ml-1, with detection limits of 0.03 and 0.05 microgram ml-1 for the cis- and trans-isomers of permethrin, respectively. The method had a recovery rate of about 70% and a relative standard deviation of less than 13%. Results suggest that this procedure provides a rapid and sensitive alternative method to those currently available.

Adsorption↗
PubMed2004

Metabolism of the dihydropyridine calcium channel blockers mebudipine and dibudipine by isolated rat hepatocytes.

The prototype 1,4-dihydropyridine (1,4-DHP) nifedipine, indicated for the management of hypertension and angina pectoris, has drawbacks of rapid onset of vasodilating action and a short half-life. Several newer analogues have been designed to offset these problems and these include mebudipine and dibudipine. These analogues contain t-butyl substituents that have been selected to alter the fast metabolism without altering pharmacological activity. In this study, the metabolism of mebudipine and dibudipine by isolated rat hepatocytes has been investigated. These compounds were extensively metabolized in 2 h by oxidative pathways, analogous to those known for nifedipine, and by O-glucuronidation after hydroxylation of the t-butyl substituents. The in-vitro half-lives of mebudipine (22 +/- 7.1 min) and dibudipine (40 +/- 9.8 min) were significantly longer than that of nifedipine (5.5 +/- 1.1 min), which was investigated in parallel in this study. These newer 1,4-DHPs address the problem of the short half-life of nifedipine and have potential for further development in view of their comparable potency to nifedipine.

Angina Pectoris↗
PubMed2004

Effects of mebudipine and dibudipine, two new calcium channel blockers, on guinea-pig isolated common bile duct.

The inhibitory effects of calcium channel blockers; nifedipine and two new compounds, mebudipine and dibudipine, on contractions of isolated guinea-pig common bile duct were investigated. All the compounds tested induced a concentration-dependent reduction of the amplitude of contractile response to electrical stimulation and all the compounds displaced concentration-response curve of calcium chloride to the right in a concentration-dependent manner. The pIC50 values for these compounds acting on electrically stimulated common bile duct were calculated as: dibudipine: 8.50 +/- 0.17; mebudipine: 8.27 +/- 0.20; nifedipine: 7.96 +/- 0.07. The compounds also antagonized the contractile response of K+-depolarized guinea-pig common bile duct to cumulative concentration of calcium. However the inhibitory effect of these compounds were not significantly different.

Animals↗
PubMed2003

Histochemical assessment of nitric oxide synthase activity in aortic endothelial cells of streptozotocin-induced diabetic rats.

Impaired endothelium-dependent relaxation of blood vessels is a common feature in diabetes, but the exact underlying mechanisms have not yet been clarified. In present study, endothelium-dependent vasorelaxation of aortic rings were evaluated in vitro in streptozotocin (STZ)-induced diabetic and age-matched control rats. Moreover, nitric oxide synthase (NOS) activity of aortic endothelial cells was assessed in both diabetic and healthy rats using histochemical staining for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity. The results showed a significant decrease of endothelium-dependent relaxation in response to acetylcholine (ACh) in diabetic rings, compared with controls, that was accompanied by a remarkable attenuation of NOS activity in diabetic sections of rat aorta stained for NADPH-diaphorase. Furthermore, a membrane disruption of some endothelial cells was also observed in all diabetic sections. It can be concluded that a decrease in NOS activity together with a disruption of endothelial cell membrane play a major role in endothelial dysfunction observed in diabetes.

Journal Article↗
PubMed2003

Interaction of noscapine with the bradykinin mediation of the cough response.

Angiotensin Converting Enzyme Inhibitors (ACEI) like captopril and enalapril, can induce persistant cough in man. Noscapine, an antitussive alkaloid, can be used to suppress ACEI-induced cough. Some workers have suggested a role for bradykinin in precipitation of ACE-induced cough. Work carried out in our laboratory has shown noscapine to be a non-competitive inhibitor of bradykinin in guinea pig ileum. It is therefore possible that noscapine suppresses cough by blocking the effect of bradykinin receptor activation in the airways. Guinea pigs were placed in a cough-chamber connected to an air pump and a pressure transducer. Capsaicin was sprayed into the chamber and cough was recorded as a distinctive change in air pressure inside the cough-chamber. Animals treated with 1 mg/kg captopril and enalapril for 7 days, showed increased cough response. Ten microgram/kg FR190997, a non-peptide agonist of the bradykinin B2 receptor, also increased the cough response. Noscapine at 0.5, 1 and 2 mg/kg was able to reverse the effects of ACEI and FR190997. Naloxone, a specific opioid receptor inhibitor, did not block the antitussive effects of noscapine in enalapril or FR190997 treated guinea pigs. This antitussive effect of noscapine is not mediated via the mu, kappa or delta opioid receptors. It is therefore possible that noscapine exerts its antitussive action by interfering with the bradykinin cough mediation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

The effect of mebudipine and dibudipine, two new Ca2+ channel blockers, in comparison with nifedipine on Ca2+ spikes of F1 neuronal soma membrane in Helix aspersa.

Mebudipine and dibudipine are two new dihydropyridine (DHP) Ca2+ channel blockers that have been synthesized by Mahmoudian et al. (1997). In previous studies, they showed considerable relaxant effect on vascular and ileal smooth muscles. These two compounds also reduced the contraction force of rat left atrium (20, 22). In the present study, we attempted to compare the inhibitory actions of these new DHPs and nifedipine on the high threshold Ca2+ spikes of F1 neuronal soma membrane in the subesophageal ganglia of Helix aspersa, using current-clamp method. At a concentration of 1 microM, two new DHP compounds (mebudipine and dibudipine) were tested for their L-type Ca2+ channel blocker activity. Both compounds reversibly reduced the peak amplitude of action potential and after hyperpolarization potential and markedly decreased the duration of Ca2+ spikes. The most potent of these DHPs was mebudipine. Neither the two new DHPs nor nifedipine changed the resting membrane potential in a statistically significant way.

4-Aminopyridine↗
PubMed2003

Reduction of the prenatal hypoxic-ischemic brain edema with noscapine.

Cytotoxic free radicals and release of several neurotransmitters such as bradykinin contribute to the pathogenesis of hypoxic-ischemic brain damage. We have studied the efficacy of noscapine, an opium alkaloid and a bradykinin antagonist, in reducing post-hypoxic-ischemic damage in developing brain of 7-d-old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was produced by legation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before hypoxia the rat pups received noscapine (dose = 0.5-2 mg/kg) or saline. Pups were scarified at 24 h post recovery for the assessment of cerebral damage by histological methods. Our results showed that noscapine was an effective agent in reducing the extent of brain injury after hypoxic-ischemic insult to neonatal rats. Therefore, it is concluded that noscapine may be a useful drug in the managements of patients after stroke.

Animals↗
PubMed2001

Effect of smoking on single dose pharmacokinetics of phenobarbital.

In order to determine interaction of smoking with single dose pharmacokinetics of phenobarbital, a 60 mg tablet of the drug was given to 12 healthy male subjects in two groups (6 smokers and 6 non-smokers) in a double blind study. An HPLC method using UV detection was developed to assess phenobarbital in plasma of the subjects. Pharmacokinetic parameters were calculated and compared in the two groups. Pharmacokinetic parameters of the two groups were not significantly different in the two groups (p<0.05). The results show no considerable effect of cigarette smoking on phenobarbital pharmacokinetics, which is in agreement with enzyme studies performed previously.

Adult↗
PubMed2001

Efffect of noscapine, the antitussive opioid alkaloid, on bradykinin-induced smooth muscle contraction in the isolated ileum of the guinea-pig.

Bradykinin (BK) and related kinins are autocoid peptides that play integral roles in many pathophysiological processes such as cough. In this study, the inhibitory effect of noscapine, the antitussive opioid alkaloid, on BK receptors, was tested in the guinea-pig ileum. Contractions of the isolated ileum of the guinea-pig in response to BK were inhibited by noscapine (10-1,000 nM) in a concentration-dependent manner. Concentration-response curves (CRCs) to BK were slightly shifted to the right with a concomitant decrease in the maximum effect. A pA2 value of 6.68 was calculated for noscapine. The slope of the Schild plot of the antagonism was found to be 0.56. Noscapine had no effect on contractions induced by KCl, acetylcholine, histamine, 5-hydroxy tryptamine or angiotensin II. In conclusion, noscapine has a specific antagonistic effect on BK receptors and the mode of inhibition was found to be non-competitive.

Animals↗
PubMed2000

Homology-based molecular modelling of PLP-dependent histidine decarboxylase from Mmorganella morganii.

The 3-D structural information is a prerequisite for a rational ligand design. In the absence of experimental data, model building on the basis of a known 3-D structure of a homologous protein is at present the only reliable method to obtain structural information. A homology model building study of the pyridoxal 5'-phosphate (PLP)-dependent histidine decarboxylase from Morganella morganii (HDC-MM) has been carried out based on the crystal structure of the aspartate aminotransferase from Escherichia coli (AAT-EC). The primary sequences of AAT-EC and HDC-MM were aligned by automated alignment procedure. A 3-D model of HDC-MM was constructed by copying the coordinates of the residues from the crystal structure of AAT-EC into the corresponding residues in HDC-MM. After energy-minimization of the resulting 3-D model of HDC-MM, possible active site residues were identified by fitting the substrate (l-histidine) into the proposed active-site. In our model, several residues, which have an important role in the AAT-EC active-site, are located in positions spatially identical to those in AAT-EC structure. The back-bone of the modelled active site pocket is constructed by residues; Gly-92, Gly-93, Thr-93, Ser-115, Asp-200, Ala-202, Ser-229 and Lys-232 together with residues Asn-8, His-119, Thr-171, His-198, Leu-203, His-231, Ser-236 and Ile-238. In the ligand binding site, it appears that the HDC-MM model will position l-histidine (substrate) in the area consisting of the residues; Glu-29, Ser-30, Leu-38, His-231 and Lys-232. The nitrogen atom of the imidazole ring (N2) of the substrate is predicted to interact with the carboxylate group of Ser-30. The alpha-carboxylate of histidine points toward the Lys-232 to have electrostatic interaction with its side chain nitrogen atom (N(Z)). In conclusion, this combination of sequence and 3-D structural homology between AAT-EC and HDC-MM model could provide insight in assigning the probable active site residues.

Amino Acid Sequence↗
PubMed2000

A study on the teratogenic and cytotoxic effects of safflower extract.

In recent years, the use of carthami flos (the flowers of Carthamus tinctorius L.) as a coloring and flavoring agent has increased as a food additive in Iran. In order to evaluate its safety, the teratogenic effects of carthami flos on the central nervous system development in mice was investigated. Furthermore, its cytotoxic effect on the rat nervous cell culture was studied to complete safety evaluations. For teratogenic studies, after natural mating, pregnant mice were divided into test and control groups. The groups were treated with different dosage regimens of aqueous carthami flos extract during 0-8 days of gestation. Embryos were then isolated at the 13th gestation day and evaluated for macroscopic, microscopic and morphometric characteristics. The results showed that in higher doses (1.6 and 2 mg/kg/day) the embryos were absorbed, whereas with lower dose (1.2 mg/kg/day) changes in external, internal and longitudinal diameters, open neuropore, changes in cellular orientation and cellular degeneration were observed. The results obtained from cytotoxic assay also demonstrated a concentration-dependent cytotoxic effect of carthami flos extract. It is concluded that the use of carthami flos as a food additive should be reconsidered.

Animals↗
PubMed2000

Coexistence of at least three distinct beta-adrenoceptors in human internal mammary artery.

The internal mammary artery (IMA) is currently the preferred conduit for myocardial revascularization. However, perioperative vasospasm and a hypoperfusion state during maximal exercise may limit its use as a bypass graft. The mechanism of spasm has not been clearly defined. Since beta-adrenoceptor activation plays a major role in vasorelaxation, the present study was carried out to investigate the beta-adrenoceptor responsiveness of human IMA smooth muscle. Isoproterenol produced a concentration-dependent relaxation in endothelium-denuded IMA segments, precontracted with phenylephrine (maximal relaxation 46.33+/-5.45%). Atenolol (10(-6)M) and propranolol (2x10(-7)M) inhibited isoproterenol-induced relaxation. While atenolol produced partial inhibition, propranolol caused a complete inhibition in a majority of the segments and a partial inhibition in a minority. BRL 37344, a selective beta 3-adrenoceptor agonist, produced a concentration-dependent relaxation in phenylephrine-precontracted rings of endothelium-denuded IMA (maximal relaxation 40.35+/-4.07%). Cyanopindolol, a beta-adrenoceptor partial agonist, produced a marked relaxation (58.65+/-6.2%) in endothelium-denuded IMA rings, precontracted with phenylephrine. Cyanopindolol-induced relaxation was resistant to blockade by propranolol (2x10(-7)M). Spontaneous contractions of IMA rings were also observed in some cases that were inhibited by isoproterenol and BRL 37344. This observation implies the important role of beta-adrenoceptor activation in prevention of human IMA spasm. The results obtained in present study indicate that human IMA smooth muscle possesses an atypical beta-adrenoceptor together with beta1- and beta2-adrenoceptors. Regarding the relaxation induced in IMA rings by adding BRL 37344, the possible identical entities of IMA atypical beta-adrenoceptors and beta 3-adrenoceptors are suggested.

Adrenergic beta-Agonists↗
PubMed2000

Correlation between ACE activity and mean blood pressure in Iranian normotensive subjects after oral administration of a single dose of enalapril.

Relationship between serum ACE activity and mean blood pressure (MAP) after administration of a single oral dose of the ACE inhibitor enalapril 10 and 20 mg tablets was investigated in 19 Iranian normotensive male subjects. Enalapril at doses, which maximally inhibit ACE activity, reduced MAP dose dependently. The t(max) of ACE inhibition decreased significantly by increasing the enalapril doses, but t(max) of MAP reduction did not change by increasing the dose. The AUC (area under the curve) of ACE inhibition versus time was significantly larger in 20 mg enalapril group compare to 10mg enalapril group (p<0.001). A significant correlation was found between log of residual ACE activity and MAP (r=0.4927; p<0.001). It is concluded that in Iranian normal subjects, after administration of a single oral dose of enalapril, MAP related to residual ACE activity.

Administration, Oral↗
PubMed1999

Atypical beta-adrenoceptors of rat thoracic aorta.

The possible existence of atypical beta-adrenoceptors in vascular smooth muscle of rat isolated thoracic aorta was investigated. Isoprenaline (10(-8)-10(-4) M) produced concentration-dependent relaxation of phenylephrine (10(-5) M) precontracted rings of endothelium-denuded rat aorta in vitro. Isoprenaline-induced relaxation was resistant to blockade by atenolol (10(-6) M). But, propranolol (2 x 10(-7) M) caused a non-competitive inhibition and SR 59230A (6.6 x 10(-6) M), a beta3-adrenoceptor selective antagonist, failed to produce additional antagonism in presence of propranolol. BRL 37344 (10(-8)-10(-4) M), a beta3-selective agonist, did not relax ring segments precontracted with phenylephrine (10(-5) M) in the absence of endothelium. The non-conventional partial agonist (-)-cyanopindolol (5 x 10(-6)-10(-4) M) induced a marked relaxation in phenylephrine (10(-5)M) precontracted aortic rings without endothelium. This vasodilation was resistant to blockade by propranolol (2 x 10(-7) M) and SR 59230A (10(-5) M). Salbutamol (10(-8)-10(-4) M) produced concentration-dependent relaxation in isolated endothelium-denuded aortic rings precontracted with phenylephrine (10(-5) M). Propranolol (2 x 10(-7) M), but not atenolol (10(-6) M), inhibited this relaxant response. It is concluded that in endothelium-denuded thoracic aorta, salbutamol acts through beta2-adrenoceptors whereas isoprenaline seems to activate both beta2-adrenoceptors and an atypical beta-adrenergic receptor. This atypical beta-adrenoceptor is distinct from putative beta3-adrenoceptor and maybe resembles the reported fourth cardiac beta-adrenoceptor.

Adrenergic beta-Agonists↗
PubMed1999

Effects of mebudipine and dibudipine, two new calcium-channel blockers, on rat left atrium, rat blood pressure and human internal mammary artery.

Mebudipine and dibudipine are two new dihydropyridine calcium-channel blockers that have been synthesized in our laboratory. In a previous study, they showed considerable relaxant effect on vascular and ileal smooth muscle. Here, the pharmacological effects of mebudipine and dibudipine on isolated rat left atrium, rat blood pressure and isolated human internal mammary artery are described. Results are compared with those obtained for nifedipine. Mebudipine and dibudipine reduced contraction force of rat left atrium (pIC30 values: 5.37+/-0.13 and 5.49+/-0.15, respectively) but their negative inotropic effects were significantly weaker than that of nifedipine (pIC30 value: 6.63+/-0.11). Mebudipine and dibudipine lowered rat blood pressure. The hypotensive effect of mebudipine was similar to that of nifedipine while dibudipine was weaker than nifedipine. It was found that the half-life of the hypotensive action of dibudipine (41.91+/-3.77 min, 31.13+/-2.26 min and 28.20+/-4.37 min at 2, 4 and 8 mg kg(-1) orally administered doses, respectively) was longer than that of nifedipine (11.85+/-2.88 min, 16.65+/-2.42 min and 14.03+/-0.10 min at the same doses, respectively). Also, it appeared that mebudipine had a slower rate of absorption compared with nifedipine (the time to reach peak hypotensive action at 2, 4 and 8 mg kg(-1) orally administered doses were, respectively, 24.00+/-6.96 min, 23.75+/-2.39 min and 15.00+/-2.04 min for mebudipine and 7.80+/-0.86 min, 13.75+/-3.15 min and 833+/-0.88 min for nifedipine). The two new compounds, as well as nifedipine, relaxed KCl-treated isolated human internal mammary artery (pEC50 values; 7.87+/-0.12, 7.22+/-0.24 and 7.67+/-0.12 for mebudipine, dibudipine and nifedipine, respectively). The relaxant effects of mebudipine and dibudipine did not show any significant difference compared with that of nifedipine. It is concluded that these new compounds are weak cardiodepressants and, with due attention to its significant vasorelaxant action, mebudipine is a vasoselective compound. In addition, these two compounds have potent blood pressure lowering effects. Also, their vasorelaxant action can be reproduced in human vascular preparations.

Animals↗