QSAR of inhibition of monoamine oxidase by substituted phenylalkylamines in vitro and in various neurons in vivo.
Explore the source record for details and available documents.
Aniline Compounds↗
Biomedical subjects
M Mahmoudian
Publications and source records attributed to M Mahmoudian.
Conformational transitions in N-linked oligosaccharides.
An assignment strategy involving 1H-1H correlated spectroscopy (COSY), relayed correlation spectroscopy (RECSY), nuclear Overhauser effect spectroscopy (NOESY), and triple quantum filtered correlated spectroscopy (TQCOSY) is described for six related N-linked oligosaccharides. These are of three "types", i.e., complex, bisected complex, and oligomannose. Using spin-spin coupling constant data derived from these assignments, together with semiempirical quantum mechanical energy calculations, we have examined the rotamer distributions at the Man alpha 1-6Man beta-linkage in each structure, and additionally at the Man alpha 1-6Man alpha-linkage in oligomannose oligosaccharides. We show that while several primary sequence differences are "passive", certain key residues modulate the orientation of the alpha 1-6 arms. These residues may be proximal or distal to the site of the conformational change. There is no direct correlation between these perturbations and the oligosaccharide type. These data are discussed in terms of the proposed recognition function of oligosaccharides in biological systems.
Animals↗
QSAR of binding of dihydropyridine-type calcium antagonists to their receptor on ileal smooth muscle preparations.
Quantitative structure-activity analysis (Hansch analysis) is applied to elucidate the structural requirement for the binding of dihydropyridine-type calcium antagonists (DHPs) to their receptor in the guinea-pig ileal muscle preparations. It is found that various steric (B1, L), electronic (sigma) and hydrophobic (pi) parameters or their combinations correlate well with the potency of various DHPs to inhibit the binding of [3H]nitrendipine to the microsomal preparations of the guinea-pig ileal muscle. The potency of DHPs increases with the minimum width (B1) of substituent at ortho- or meta-positions, but decreases with the increase in the length of substituent at the meta-position. The potency of DHPs decreases with the increase in both minimum width or length of substituent at the para-position and the optimal values were found to be those for hydrogen. The hydrophobicity (pi) of substituents at different positions in the 4-phenyl ring affects the potency differently, indicating that a different environment exists around each position at the binding site. From the slopes of the pi variable in the regression equations, it is concluded that the receptive environment of the ortho-position of the 4-phenyl ring of DHPs is lipophilic, and for that of the para-position hydrophilic. A good correlation is also observed between the Hammett electronic parameter (sigma) and biological activity of meta-substituted DHPs. It is suggested that in the binding of the substituted 4-phenyl DHPs to their receptor, both electronic and hydrophobic interactions should be considered.
Animals↗
In vitro binding of dantrolene to sarcoplasmic reticulum of rabbit skeletal muscle.
Dantrolene upon binding to microsomes containing sarcoplasmic reticulum of rabbit thigh muscle exhibits a fluorescence with emission at 490 nm, which shows a blue shift of 35 nm compared with its fluorescence in ethylacetate. Using fluorescence techniques, dantrolene binding to microsomes isolated from rabbit thigh muscle was investigated. From Scatchard plots of binding studies, the association constant (Kass) and the number of binding sites of dantrolene to sarcoplasmic reticulum were calculated, which was found to be 9.6 X 10(4) M-1 and 1.71 mumole/g of membrane proteins, respectively. In the presence of verapamil (1.25 X 10(-4) M), another calcium antagonist, the binding of dantrolene to microsomes was enhanced. However, at a high concentration of verapamil (3.75 X 10(-4) M), the Scatchard plot of dantrolene binding was found to be biphasic.
Animals↗
In vitro binding of dantrolene to bovine serum albumin and rabbit red blood cell ghosts.
The binding of dantrolene to rabbit red blood cell (RBC) ghosts and bovine serum albumin as models of receptor sites was studied using fluorescence techniques. Dantrolene upon binding to rabbit RBC ghosts and bovine serum albumin showed fluorescence with emission maxima at 495 and 500 nm, respectively. Dantrolene bound to rabbit RBC ghosts with an association constant of 6.06 X 10(4) M-1 and there were 2.4 X 10(6) dantrolene binding sites per ghost. The binding of dantrolene to bovine serum albumin showed an anomaly with respect to dantrolene concentration. Dantrolene at concentrations of 1.25-3.75 microM bound to bovine serum albumin with an association constant of 1.72 X 10(4) M-1 and there were 1.078 binding sites/mol bovine serum albumin. The higher affinity of dantrolene toward blood cells was confirmed by studying the distribution of dantrolene between blood cells and plasma after a single i.p. injection of dantrolene sodium (3 mg/kg) to albino rabbits. It was found that the concentration of dantrolene in rabbit blood cells was 2.76 times that of plasma.
Animals↗
Effect of dantrolene sodium on the contractility of rabbit jejunum in vitro.
The effect of dantrolene sodium on the spontaneous contractions of rabbit jejunum was studied in vitro. Dantrolene sodium (4.5 x 10(6) to 4.5 10(4) M) reversibly decreased the amplitude of contractions in a dose-dependent manner. ED50 was found to be about 7.9 x 10(-5) M. Its effect was biphasic in that a period of potentiation preceded that of suppression of contractions. Lowering or increasing (2.5 fold in each direction) the calciumm concentration of bathing media did not affect the suppression of contraction caused by dantrolene sodium to any significant degree. Caffeine but not quinine was found to be able to restore the activity of the intestine to normal after a 50% inhibition caused by dantrolene sodium. Dantrolene sodium, verapamil and nifedipine were able to shift the dose-response curves of calcium in potassium-polarized rabbit jejunum to the right and pA2 values were found to be 4.18, 7.76 and 8.47 respectively. These data indicate that the effect of dantrolene on smooth muscle is mediated via inhibition of calciu movement across the membrane.
Animals↗
High-performance liquid chromatographic assays for studying the formation of iodotyrosines and iodothyronines in sheep thyroid peroxidase preparations.
Explore the source record for details and available documents.
Animals↗
The uptake of [35S]methimazole by sheep thyroid slices in vitro.
Explore the source record for details and available documents.
Animals↗
High performance liquid chromatography of mebudipine: application to pharmacokinetic study.
PURPOSE: To develop a high performance liquid chromatography system for the determination of a new 1,4-dihydropyridine, mebudipine, in rabbit plasma. METHODS: To 1 ml of rabbit plasma was added internal standard (dibudipine) and 0.5 ml of 1 M NaOH. Mebudipine and internal standard were extracted to 5 ml ethyl acetate, evaporated under slow stream of nitrogen. The residue was reconstituted in 200 microl mobile phase and 20 microl of aliquots were injected into a HPLC system equipped with 4.6 x 250 mm i.d. C18 analytical column. Mobile phase consisted of methanol (70%), water (25%) and acetonitril (5%) and its flow rate was 1 ml/min. RESULTS: There were no interfering peaks from endogenous components in blank plasma chromatograms. Standard curves were linear (r(2)>0.99) over 10 to 500 ng/ml. The extraction efficiency was >90% and the minimum quantifiable concentration was 10 ng/ml (CV<10%). CONCLUSION: A suitable, convenient and simple HPLC assay for pharmacokinetic study of mebudipine in rabbits was developed.
Animals↗
A quantitative thin layer chromatography method for determination of theophylline in plasma.
A simple assay method for theophylline in plasma using thin layer chromatography (TLC) was developed. The method involves extraction of the drug and internal standard (acetaminophen) by chloroform-isopropanol (75:25) followed by separation on TLC silica plates using a mixture of acetic acid, isopropanol, toluene (1: 12: 6), as the eluting solvent. Both peak height ratios and peak are ratios showed high correlation coefficient (r>0.98, p<0.001). However we used peak heights for the determinations. Within-day and between-day coefficients of variation were less than 4.4% and 7.8% respectively. The assay proved inexpensive, accurate and reproducible with a limit of detection of 100 ng/ml that makes it suitable for bioavailability studies.
Biological Availability↗
Determination of niacinamide with cyanogen bromide and sodium 1-phenyl-2,3-dimethyl-5-pyrazolone-4-methylaminomethanesulfonate.
Explore the source record for details and available documents.
Cyanogen Bromide↗
Inhibitory action of aminoglycoside antibiotics on the electrically induced release of opioid peptides in the guinea-pig ileum in vitro.
The effect of aminoglycoside antibiotics upon the electrically induced release of endogenous opioid peptides from the guinea-pig ileum was studied in vitro. Stimulation of guinea pig ileum at 10 Hz in normal Tyrode solution resulted in the naloxone sensitive depression of the twitch contractions of this muscle. Addition of aminoglycosides during 10 Hz stimulation diminished this naloxone sensitive depression in a dose dependent manner. IC50s of this effect of streptomycin, neomycin, kanamycin and gentamicin were found to be 2.54, 2.29, 1.36 and 0.7 mg/ml respectively. A 3.5 fold increase in the calcium concentration of media during 10 Hz stimulation significantly reversed the effect of aminoglycosides. It is concluded that aminoglycoside antibiotics exert their effect by interfering with trans-membrane movements of calcium at the nerve endings which is required for the electrically induced release of opioid peptides.
Aminoglycosides↗