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Biomedical subjects

D R Fuller

Publications and source records attributed to D R Fuller.

10 recordsLinked to original sources
PubMed2001

Metabolism of vanoxerine, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine, by human cytochrome P450 enzymes.

Vanoxerine (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine; GBR12909) is a promising agent for the treatment of cocaine dependence. Knowledge of the major pathway for GBR12909 metabolism is important for prediction of the likelihood of drug-drug interactions, which may affect the therapeutic clinical outcome, when this agent is used in cocaine-dependent individuals receiving multiple drug therapy. We studied biotransformation of GBR12909 in human liver microsomes (n = 4), human hepatocytes, and microsomes containing cDNA-expressed human P450 isoforms with GBR12909 concentrations within the range of steady-state plasma concentrations detected in healthy volunteers. A high-pressure liquid chromatography assay was used to measure parent GBR12909 and its primary metabolite. GBR12909 was metabolized by human liver microsomes, hepatocytes, and cDNA-expressed human P450s to a single metabolite. Ketoconazole, a selective inhibitor of CYP3A, reduced GBR12909 biotransformation in human liver microsomes and primary hepatocytes by 92 +/- 2 and 92.4 +/- 0.4%, respectively. Quercetin (an inhibitor of CYP2C8/3A4) was a less effective inhibitor producing 62 +/- 22% inhibition in human liver microsomes and 54 +/- 35% in hepatocytes. Other P450 selective inhibitors did not decrease GBR12909 biotransformation more than 29% in either human liver microsomes or hepatocytes with the exception of chlorzoxazone (CYP2E1), which inhibited GBR12909 biotransformation by 71.4 +/- 18.5% in primary human hepatocytes. Ciprofloxacin (CYP1A2), sulfaphenazole (CYP2C9), quinidine (CYP2D6), chlorzoxazone (CYP2E1), and mephenytoin (CYP2C19) did not demonstrate statistically significant inhibition (p > 0.05) of GBR12909 biotransformation in liver microsomes. cDNA-expressed P450 3A4 metabolized GBR12909 to a greater extent than 2C8 and 2E1. These data suggest the possibility that multiple P450 isoforms may be involved in human GBR12909 metabolism but that CYP3A appears to be the major enzyme responsible for human GBR12909 biotransformation.

Biotransformation↗
PubMed1992

Effects of configuration on the paired-associate learning of blissymbols by preschool children with normal cognitive abilities.

Translucency appears to be a potent variable in the learning of Blissymbols by preschool children with normal cognitive abilities. Complexity does not appear to influence learning for these individuals when there is a concurrent condition of high translucency. However, a condition of high complexity seems to enhance the learnability of Blissmbols having low translucency. For the present experiment, an attempt was made to determine if symbol configuration affects the learning of highly complex Blissymbols that bear little relationship to their referents. A paired-associate learning paradigm was used to present 30 Blissymbols to 20 cognitively normal preschool children. These symbols were evenly divided into superimposed and nonsuperimposed groups. Results indicated that the children learned more superimposed symbols than their nonsuperimposed counterparts. The implications of this finding for the teaching of Blissymbols are discussed.

Child Language↗
PubMed1969

A quantitative analysis of the responses of certain dorsal horn neurones to mechanical stimulation of the large foot pad in cats.

1. Responses of single units in the dorsal horns of the spinal cords of cats to mechanical stimulation of the large foot pad have been recorded.2. The observations made with different single stimuli belonging to the set under different conditions of excitability have included: the numbers of impulses per response, their means and variation; the frequency distributions of impulse numbers; the time distribution of activity during a response and in particular the probability of an impulse occurring in each successive time interval.3. The observations with two stimuli were designed to measure the [ill] of the whole response contributed by the second stimulus and [ill] relate the size of this contribution to the interval between the stimuli and their distance apart.4. The results are discussed and it is concluded that the observed transformations allow representations of successive events to exist at the same time and that the purpose of the transformation may therefore be to allow particular types of interaction between successive events. A model of mechanism which is consistent with many of the observations is also discussed.

Animals↗
PubMed1966

The relation between mechanical displacements applied to a cat's pad and the resultant impulse patterns.

1. A way of determining an approximation to the distribution of impulses resulting from certain mechanical stimuli to a cat's pad is described. In essence this consists of calculating the results from a model of the way in which the impulses are set up.2. The results of these calculations have been compared with results of experiments of a type different from those on which the calculations were based. Total numbers of impulses have been found by measuring mass action potential areas under appropriate conditions. The ranges of absolute numbers of impulses are similar for both calculated and direct results. The curves relating changes of number to changes of stimulus strength are similar in the two cases as are the effects of changing the position of the stimulus. Similar comparisons using two pulses at different times and distances apart have also been made. The over-all time distribution has been checked by reconstructing mass action potentials from the calculations and comparing these with those observed.3. The calculations were carried out with values which were chosen in advance and which were based on previous experimental evidence; the results were in reasonable agreement with the experimental checks. It is therefore concluded that the results are a sufficiently good approximation to the neural responses of cats' pads to this type of stimulation to justify applying them in answering the questions posed in the Introduction.

Animals↗