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Biomedical subjects

T Kometani

Publications and source records attributed to T Kometani.

34 records · Page 2Linked to original sources
PubMed1979

Optical resolution of some homobenzomorphan derivatives and their pharmacological properties.

Racemic 1,4-dimethyl- (1), 1,4,12 alpha-trimethyl- (2), and 1,4,12 beta-trimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine (3) have been optically resolved. The analgesic potency and physical-dependence capacity of the optical isomers and their racemic parents were determined. The levo isomers of compounds 2 and 3 were analgesically much more potent than the dextro isomers and were equipotent with morphine. Optical resolution gave no effect on the activity of compound 1. None of the optical isomers and the racemates suppressed the morphine-withdrawal syndrome in the monkey.

Analgesics↗
PubMed1978

Ionic permeability of sarcoplasmic reticulum vesicles measured by light scattering method.

The volume change of sarcoplasmic retriculum vesicles was followed by measuring the light scattering intensity. When the salt concentration of the suspension of sarcoplasmic reticulum vesicles was increased by using a stopped flow apparatus, the light scattering intensity rapidly increased at the beginning and then decreased. The fast increase in the light scattering intensity is caused by the decrease of the volume of sarcoplasmic reticulum vesicles due to the outflow of water. The following decrease in the light scattering intensity is caused by the increase of the volume due to the inflow of the solutes and water. From the former and the latter rates, the permeation times of water and the solutes could be calculated, respectively. According to the same method, permeation times of various salts were determined. The rate of the inflow of the salts was dependent on the movement of the slower ions, that is, ions move as a pair. In the case of potassium salts, an increase in the permeation rate of the salts was observed when valinomycin was added to the membrane suspensions. From these experiments, as a measure of permeability, half permeation times of various ions and molecules were determined. The following are typical results: water 0.1, Li+ 36, Na+ 26, K+20, Rb+ 16, Cl- 0.4, methanesulfonate 20, phosphate 10.5, oxalate 40 in seconds at room temperature. As a whole, sarcoplasmic reticulum was found to be an anion permeable membrane.

Animals↗
PubMed1978

Synthesis and analgetic activity of some benzomorphan analogues.

The benzomorphan analogues, 8-hydroxy-3-methyl-2,3,4,5-tetrahydro-1,4-methano-1H-3-benzazepine (1), 8-hydroxy-2-methyl-2,3,4,5-tetrahydro-1,4-methano-1H-2-benzazepine (2), 9-hydroxy-2-methyl-1,2,3,4,5,6-hexahydro-1,5,-methano-2-benzazocine (3), and 10-hydroxy-2-methyl-2,3,4,5,6,7-hexahydro-1,6-methano-1H-2-benzazonine (4), have been synthesized in order to evaluate their analgetic activity. Only slight analgetic activity was found in any of these compounds. The importance of nitrogen to aromatic ring distance for the analgetic-receptor interaction is discussed.

Analgesics↗
PubMed1977

9-hydroxy-1,2,3,4,5,6-hexahydro-1,5-methano-3-benzazocine derivatives as analgesics.

Three 1,3-dimethyl-9-hydroxy-1,2,3,4,5,6-hexahydro-1,5-methano-3-benzazocine derivatives (7-9) have been synthesized and tested as analgesics. The synthesis of these compounds involved conversion of 1-methyl-7-methoxy-beta-tetralone (1) by Mannich reaction with MeNH2 and HCHO to give the 11-ketone 2, from which 7,8, and 9, respectively, were obtained. These compounds have analgesic activity, and 7 was found to be comparable to codeine.

Analgesics↗
PubMed1977

B/C-cis- and -trans-1,3,4,9,10,10a-Hexahydro-2H-10,4a-methanoiminoethanophenanthrene (homo- and homoisomorphinan) derivatives as analgesics.

N-Alkyl derivatives of B/C-cis- and B/C-trans-6-hydroxy-1,3,4,9,10,10a-hexahydro-2H-10,4a-methanoimino-ethanophenanthrene have been prepared. The analgesic potency and physical dependence capacity of these compounds were determined. The N-methyl derivatives were analgesically equipotent with morphine. None of these compounds except the N-methyl-B/C-trans isomer 2b suppressed or precipitated the abstinence syndrome. Compound 2b was a narcotic agonist. The N-methyl-B/C-cis compound 2a appears to warrant further examination for its potential as a potent analgesic having no physical dependence liability.

Analgesics↗
PubMed1977

Quantitative determination of erythrocyte zinc protoporphyrin.

An elevated zinc protoporphyrin (ZPP) level in blood is indicative of lead poisoning (as well as iron-deficiency anemia) and is the basis for certain fluorometric screening tests. The calibration of such test protocols and instruments requires ways to reliably determine absolute ZPP concentrations in blood. Two such methods are described: one is an ethanol extraction method and the other a fluorometric addition method using detergent hemolyzed blood. A careful determination of the molar extinction coefficient of ZPP gives EmM=161 in pyridine. Corrections are offered for a previously published protocol for determining the ZPP concentration from the fluorescence intensity of diluted blood. The choice of units for expressing the ZPP concentration in blood is discussed, as is the absorbance correction in quantitative fluorometry of samples which are not optically thin at the excitation wavelength.

Erythrocytes↗
PubMed1976

10-Hydroxy-4-methyl-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine derivatives (homobenzomorphans) as analgesics.

Six 10-hydroxy-4-methyl-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine derivatives 17a-f have been synthesized as potential analgesics. The synthesis of these compounds involved conversion of 4-(2-dimethylaminoethyl)-6-methoxy alpha tetralone derivatives 12a-f to their N-methyl analogues and the subsequent intramolecular mannich reaction with formaldehyde to give the 7-keto C-ring homobenzomorphans 14a-f from which 17a-f, respectively, were obtained. Compounds 17a-f are as potent as morphine as analgesics (mice).

Analgesics, Opioid↗
PubMed1975

Acetylcholine-binding substance extracted by using organic solvent and acetylcholine receptor of electric organ of Narke japonica.

1. Proteolipid was extracted from the electric organ of Narke japonica by using chloroform/methanol (2:1, v/v). This extract was separated into acetylcholine-binding and non-binding substances by column chromatography. However, acetylcholine-binding substances did not show the characteristic properties of protein. 2. The membrane fragments of the electric organ were separated into three main parts by sucrose density gradient centrifugation. From the heaviest, the fractions were acetylcholine receptor rich, ATPase rich, and acetylcholinesterase rich. 3. The membrane fraction having acetylcholine receptor showed the excitability, the increase of Na+ permeability by the application of cholinergic agonists. However, the acetylcholine binding substance extracted by the organic solvent was richer in the lighter fraction. This substance differed from the true acetylcholine receptor.

Acetylcholine↗
PubMed1975

2,3,4,5,6,7-hexahydro-1,6-methano-1H-3-benzazonine derivatives as analgesics.

10-Methoxy- (10) and 10-hydroxy-3-methyl-2,3,4,5,6,7-hexahydro-1H-3-benzazonine (11) have been synthesized from 7-methoxy-alpha-tetralone (1) via the 1-aminomethyl compound 4, which was converted to the amino acid derivative 7. Hydrogenation and cyclization of 7 afforded the lactam 9, which was reduced with LiAlH4, followed by N-methylation to give 10, from which 11 was obtained. Compounds 10 and 11 have analgetic activity, and the former was found to be comparable to codeine.

Analgesics↗
PubMedDate not supplied

Photoaffinity heterobifunctional cross-linking reagents based on N-(azidobenzoyl)tyrosines.

New heterobifunctional cross-linking reagents that possessed a photoactive terminus, an electrophilic terminus, and a linking arm between the two termini that had a radiolabeled, enzymatically cleavable bond were synthesized. In a model study, succinimidyl N-[N'-(4-azidobenzoyl)tyrosyl]-beta-alanate (16A) was coupled to n-butylamine (a Lys surrogate), iodinated, and cleaved with chymotrypsin in the presence of tyrosylamide to afford the desired adduct (N-(N'-(4-azidobenzoyl)-3-iodotyrosyl)tyrosinamide, thereby demonstrating the feasibility of the enzymatic cleavage. In a biochemical study, succinimidyl N-[N'-(3-azido-5-nitrobenzoyl)tyrosyl]-beta-alanate (16C) was coupled to Lys-75 of calmodulin (CaM), and the radioiodinated monoadduct was successfully photo-cross-linked, in a calcium-dependent manner, to the human erythrocyte plasma membrane Ca2+,Mg2(+)-ATPase and to a synthetic fragment (M13) containing the CaM-binding region of myosin light-chain kinase. In the latter case, densitometry readings indicated 20% cross-linking efficiency.

Affinity Labels↗
PubMedDate not supplied

Photoaffinity heterobifunctional cross-linking reagents based on azide-substituted salicylates.

Photoaffinity heterobifunctional cross-linking reagents are described that incorporate a 4-azidosalicylate group at one terminus and an N-hydroxysuccinimidyl ester at the other terminus with a "linking arm" of variable length separating the photoactive and electrophilic termini. Exposure of calmodulin (CaM) to succinimidyl N-[2-[(4-azidosalicyloyl)oxy]ethyl]suberamate (4C) led to monoadducts at Lys-21, Lys-75, and Lys-94. Separation of the monoadducts from CaM and polyadducts, radioiodination, and photolysis in the presence of human erythrocyte plasma membrane Ca2+, Mg2(+)-ATPase led to calcium-dependent cross-linking with 8% cross-linking efficiency.

Affinity Labels↗