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Biomedical subjects

E Reeder

Publications and source records attributed to E Reeder.

8 recordsLinked to original sources

2-benzazepines. 5. Synthesis of pyrimido[5,4-d][2]benzazepines and their evaluation as anxiolytic agents.

A series of 5H-pyrimido[5,4-d][2]benzazepines has been synthesized, starting from the corresponding 2-benzazepin-5-ones, and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different than that of diazepam. They are more potent than diazepam in the anti-pentylenetetrazole test and in the [3H]diazepam binding assay, yet show less activity in the inclined screen test. A pharmacological data profile is given for 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (7c). The structure-activity relationships of these potential anxiolytic agents are discussed.

Animals

2-benzazepines. 6. Synthesis and pharmacological properties of the metabolites of 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine.

The 2-benzazepine 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (1) has been selected for development as an anxiolytic agent. In support of this program, we have confirmed by chemical synthesis the structures of three in vitro (rat liver homogenate) metabolites of 1 and confirmed the structure of the major in vivo (dog and man) metabolite of 1, compound 2. Two of the metabolites, arising from hydroxylation of the pyrimidobenzazepine ring at the 5-position (2) and N-oxide formation at the 3-position of the pyrimidobenzazepine ring (3), were found to be as active as 1 in a series of pharmacological tests. The third metabolite, formed by hydroxylation of the 7-phenyl group in the 4-position (4), was found to be inactive in the same pharmacological screens.

Animals

The effect of changes in dose rate on the yield of chromosome aberrations in human lymphocytes exposed to gamma radiation.

The yield of chromosome aberrations was studied in Go human peripheral blood lymphocytes following in vitro exposure to 100, 250 and 500 rad of caesium-137 gamma radiation. The doses were given at various rates up to 400 rad per h with the longest exposures lasting for approx. 50 h. At 500 and 250 rad the dicentric yields fell by 66 and 64% when the dose rate was reduced from 400 to 10 rad per h whereas at 100 rad the reduction was only 29%. Reductions were also noted in frequency of acentric aberrations. At the higher dose rates (greater than 150 R/h) the aberration yield was constant and agreed with data published elsewhere for 3000 R/h. The dose rate at which the decline in aberration yield became apparent was dose dependent and, for dicentrics, occurred at about 150, 100 and 25 rad/h respectively for the 500-, 250- and 100-rad doses. The data are interpreted in terms of the quadratic model of aberration induction in which the dose-squared term represents dose rate dependent two-track aberrations which constitute an increasingly important component of yield as dose increases. The implications of this work for cytogenetic dosimetry are discussed.

Chromosome Aberrations

Chromosome aberration yields in human lymphocytes induced by fractionated doses of x-radiation.

Unstimulated (G0) human peripheral blood lymphocytes were exposed at 37 degrees C to doses of 200 or 500 rad of X-rays delivered in two equal fractions. The dose fractions were separated by intervals of up to 7 h in the 200 rad study and up to 48 h for 500 rad. In both studies the mean levels of dicentrics and total unstable aberrations began to decline when fractions were delivered with intervals of greater than 2 h. With 200 rad the yield had decreased to an additive baseline (i.e. equal to only twice the yield of a single 100-rad fraction) by an interval of 4 h. Following 500 rad the yield declined until 8 h and then remained 20% above the additive baseline even when 48 h separated the fractions. Possible explanations for this discrepancy are discussed. In a second experiment PHA stimulated lymphocyte cultures were exposed to 2 doses of 125 rad of X-rays up to 7 h apart in an attempt to demonstrate the late peak in aberration yields originally reported by Lane [5]. Control cultures received unsplit doses of 250 rad at the time of the corresponding second 125-rad fraction. No evidence of a late peak in dicentric yield was observed. The yield remained approximately the same irrespective of the time interval between fractions but these split dose yields were significantly different from the accompanying unsplit controls.

Chromosome Aberrations

Group evaluation: a collaborative, peer-mediated behavior management system.

The efficacy of a consensus based group-evaluation system was examined using a reversal design. Two groups of students with disabilities served as subjects. The group-evaluation system involved: (a) dividing the groups into teams; (b) having each team agree on a common rating for the group's behavior during a specified time period; (c) comparing each team's rating to the teacher's rating; and (d) delivering reinforcement to each team based on the group's behavior and the team's accuracy in rating the group's behavior. Results indicated that the group-evaluation system was an effective strategy for modifying classroom behavior.

Adolescent