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Biomedical subjects

B Jarrott

Publications and source records attributed to B Jarrott.

At least 163 records · Page 9Linked to original sources
PubMed1982

Demonstration of a S-methyl metabolite of captopril in patients undergoing chronic captopril therapy.

1. The formation of the S-methyl metabolite of captopril has been demonstrated for the first time in the urine of five patients receiving chronic captopril therapy. 2. Patients were studied following a 100 mg oral dose of captopril. 3. Excretion values for S-methylcaptopril were 0.66 mg and 0.31 mg at 0-3 h and 3-6 h postdose. Captopril excretion was at these two collections 15.5 mg and 2.3 mg, respectively.

Captopril↗
PubMed1981

Comparison of [3H]clonidine and [3H]guanfacine binding to alpha 2 adrenoceptors in membranes from rat cerebral cortex.

[3H]Clonidine and a new phenylacylguanidine antihypertensive drug, [3H]guanfacine, bind with a high affinity to alpha 2 adrenoceptors in membranes from rat cerebral cortex. Dissociation curves for [3H]clonidine binding indicated the presence of high and low affinity binding sites, whereas with [3H]guanfacine, two components could be distinguished only with difficulty; the major part of the binding being to a high affinity component. Saturation experiments revealed that both ligands bind with similar high affinity but that [3H]guanfacine labels twice the number of sites labeled by [3H]clonidine.

Animals↗
PubMed1981

High-performance liquid chromatographic analysis of captopril in plasma.

A sensitive assay is described for quantitating plasma captopril levels. Captopril is an orally active inhibitor of angiotensin-converting enzyme. Blood from patients taking this drug was collected into tubes containing edetate and ascorbic acid, and the plasma was separated by centrifugation. After addition of an internal standard, the plasma was deproteinized and the supernate was adjusted to pH 6.5 N-(1-Pyrene)-maleimide was added to derivatize captopril and an internal standard to fluorescent adducts. These derivatives then were extracted into ethyl acetate-benzene (1:1) and separated from other derivatized thiols by high-performance liquid chromatography. The sensitivity of the assay was 150 pmoles/ml. Preliminary pharmacokinetics were obtained in patients taking captopril chronically for essential hypertension. After administration of 100 mg of captopril for patients who had fasted overnight, the plasma levels rose rapidly; peak levels were obtained at approximately 37 min. Thereafter, the plasma levels declined rapidly, and the terminal half-life was approximately 40 min. In these patients, the time course of the plasma levels did not reflect changes in blood pressure, so there appeared to be no direct relationship between plasma levels of the parent compound and blood pressure changes.

Captopril↗
PubMed1980

Displacement of [3H]clonidine binding by clonidine analogues in membranes from rat cerebral cortex.

[3H]Clonidine binds to membranes prepared from rat cerebral cortex by a high affinity saturable process. Using [3H]clonidine of specific activity 5.29 Ci/mmol the Kd for the binding was 1.7 +/- 0.1 nM and the Bmax 9.4 +/- 0.6 pmol/g (n = 5). The Hill coefficient for [3H]clonidine binding to rat cerebral cortex membranes was 0.97 +/- 0.05 (r > 0.93; n = 5) indicating an absence of +ve or -ve cooperativity. The clonidine metabolites 4-hydroxyclonidine; N(2,6-dichlorophenyl)guanidine; N(2,6-dichloro-4-hydroxyphenyl)guanidine; and 2-(2,6-dichlorophenyl)iminoimidazolidine-4-one and the metabolic intermediate 2-(2,6-dichlorophenylamino)imidazole were less effective displacers of [3H]clonidine binding than the parent compound. The first three compounds were more polar and the last two less polar than clonidine as judged by their apparent partition coefficients in octanol/phosphate buffer. Seven imidazolidine derivatives with known alpha-adrenoceptor activity were potent displacers of [3H]clonidine binding: the order of potency being 14,304-18 > naphazoline > clonidine > lofexidine and tiamenidine > CP18,534 > ST600 > ST91. Five 'clonidine-like' drugs displaced [3H]clonidine binding with an order of potency guanabenz > Baya 6781 > guanfacine > clonidine > xylazine >> FLA136. Apparent partition coefficients of the displacing agents have been measured in octanol/phosphate buffer and the importance of this factor is discussed with reference to their in vivo antihypertensive potency and potency as displacers of [3H]-clonidine binding.

Animals↗
PubMed1980

Use of dopamine and prazosin combined in the treatment of cardiogenic shock.

Seventeen patients who developed cardiogenic shock after acute myocardial infarction were treated with intravenously infused dopamine. In eight of these patients a stable blood pressure was attained, but oliguria or anuria persisted, and oral treatment with prazosin was instituted. Diuresis occurred in seven of these patients, but was followed by transient hypotension associated with a rapid rise in plasma prazosin levels in three. Four patients left hospital, and there were two long-term survivors. Prazosin may be a useful adjunct to dopamine in the treatment of cardiogenic shock.

Administration, Oral↗
PubMed1980

Regional distribution of the muscarinic cholinoceptor and acetylcholinesterase in guinea pig brain.

The muscarinic receptors in membranes prepared from guinea pig brain were studied using a radiolabeled antagonist, [3H]quinuclidinyl benzilate (QNB). The apparent dissociation constant of the QNB-receptor complex (Kd) was similar in all regions, but the concentration of receptors was highest in the striatum, cerebral cortex, and hippocampus and lowest in the cerebellum. Similar distributions have been reported for other species, although the concentration of receptors in guinea pig brain is higher than in other species. Acetylcholine inhibited QNB binding with a Hill coefficient of 0.4-0.6. The concentration of acetylcholine required to inhibit binding by 50% (I50) was lowest in the brain stem and more than 10 times higher in the hippocampus. Similar results have been reported for mouse brain. The activity of acetylcholinesterase was highest in the striatum, where the concentration of muscarinic receptors is highest, but did not vary greatly in other brain regions.

Acetylcholine↗
PubMed1980

Clonidine distribution in the rat: temporal relationship between tissue levels and blood pressure response.

1. The time course of the distribution of clonidine (20 microgram/kg, i.v.) was determined in the rat by use of a sensitive and specific radioimmunoassay, and was compared with the hypotensive response following this dose. 2. Levels of clonidine were determined in tissues at 2 min, corresponding to the beginning of the hypotensive phase of the drug, and then at 10, 30 and 120 min during recovery of blood pressure to the pre-dose level. The peak tissue concentrations of clonidine were found at 2 min, after which they declined in a mono-exponential manner. The half-lives of clonidine in the various tissues were similar to the half-life of the recovery of blood pressure. 3. Regional variations in clonidine distribution in the brain were not very great; however, the half-life was longer in the corpus striatum and shorter in the cerebellum than in other brain regions. 4. Clonidine concentrations were highest in the kidney and similarly distributed between the cortex and medulla. Concentrations of the drug in other tissues approximated those in brain. 5. Although clonidine is thought to act primarily through the central nervous system, this distribution study shows that at the peak of the hypotensive response less than 2% of the injected dose is present in brain and at least equal concentrations of the drug are found in most peripheral tissues. Thus the possibility of peripheral mechanisms contributing to the hypotensive effect cannot be dismissed.

Animals↗
PubMed1980

Isolated brain microvessels: preparation, morphology, histamine and catecholamine contents.

A method for the rapid preparation of parenchymal microvessels from rat, rabbit and bovine brains is described. Light and electron microscopic examination of the isolated microvessels showed the smooth muscle and endothelial cells to be intact and substantially free of neutrophil contamination. The observation of 0.2 to 2.0 micron electron dense granules in the adventitial space associated with some of the isolated arteriolar elements and the identification of histamine in microvessel extracts is suggestive of the presence of mast cells in the microvessel preparations. Age-dependent changes in histamine content and an increased histamine content in microvessels from hypertensive rats were noted. Using a sensitive radioenzymatic assay, the catecholamine (CA) contents of microvessels isolated from cow, rat and rabbit were measured. The total CA contents of all microvessel preparations were small (< 0.35 microgram g-1) with norepinephrine being the predominant CA present. A large ratio of dopamine to norepinephrine was found in microvessels from rat and bovine brain. The possible origins of the CAs present in the isolated microvessels are discussed.

Animals↗
PubMed1980

alpha- and beta-Adrenoceptor activities of norepinephrine analogues in isolated tissues of the rat.

A range of norepinephrine analogues has been studied in rat tracheal, atrial, and aortic preparations. Isopropyl appeared to be the most favorable N-substituent for agonist action on tracheal adrenoceptors, whereas hydroxyphenylisopropyl gave highest activity on atrial adrenoceptors. Selectivity for the beta 2-adrenoceptor was improved with tertiary branching at the gamma-carbon and further increased by aromatic substitution with resorcinol or saligenin. Alpha-Adrenoceptor properties were substantially modified by N-substitution, whereas aromatic substitution was an important factor in determining beta-adrenoceptor agonist or antagonist activity at the beta-adrenoceptor. The data were consistent with norepinephrine analogues having multiple sites of attachment to the receptor membrane influencing receptor potency and selectivity. The data also suggest that compounds of this type can have actions on both alpha- and beta-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1980

Characterization of alpha-adrenoceptors in rat and guinea pig tissues using radiolabeled agonists and antagonists.

Tritium-labeled preparations of the selective alpha 2-adrenoceptor agonist, clonidine, and the selective alpha 1-adrenoceptor antagonists, prazosin and WB 4101, were examined for their suitability as ligands for receptor assay. In the rat brain, 3H-clonidine bound specifically with high affinity to membrane sites, and drug displacement studies indicated that these were alpha 2-adrenoceptors. The structural requirements for this receptor were defined by examining a range of clonidine analogues. 3H-Clonidine binding to peripheral tissues of the rat was very low, although peripheral tissues from guinea pig exhibited higher binding. Specific 3H-clinidine binding was not reduced after chemical sympathectomy, suggesting that the binding site, although having characteristics of an alpha 2-adrenoceptor, was not located presynaptically. Studies with 3H-WB 4101 in rat cerebral cortex indicated that this ligand bound to an alpha 1-adrenoceptor which was independent of the 3H-clonidine-binding site. 3H-Prazosin was a ligand for alpha 1-adrenoceptors in guinea pig brain and also in membranes from seminal vesicle. However, in the latter tissue, characterization of the binding site was hampered by a high degree of nonspecific binding (50% of total binding).

Animals↗