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Biomedical subjects

P Darcy

Publications and source records attributed to P Darcy.

16 recordsLinked to original sources
PubMed2002

The effect of lofepramine and other related agents on the motility of Tetrahymena pyriformis.

Tricyclic antidepressants (TCAs) were introduced almost 50 years ago. Whilst there is no doubt that TCAs are effective in treating depression, they are also more cardiotoxic when taken in overdose than other antidepressant groups. Lofepramine is a more recently introduced modified TCA, which in animals and man has low toxicity when compared to older TCAs. Paradoxically, lofepramine is extensively metabolised to desipramine, which has considerable toxicity, both experimentally and in overdose. The toxicity of such compounds is attributed, in part, to a membrane stabilising effect (MSA) on cell membranes. This MSA causes gross effects to the cell structure and in turn, normal cell activity. The aim of this study was to compare the MSA of lofepramine with that of desipramine and amitriptyline in order to see if this might help to explain the low toxicity of lofepramine. The local anaesthetic agent lignocaine was also studied for comparison. Each compound was enclosed in a beta-cyclodextrin to increase its solubility in aqueous medium. The extent of MSA was determined as a measure of the effect on the swimming speed of the protozoan Tetrahymena pyriformis using a video image analysis system. The IC50s for the various drugs were then correlated with their respective octanol-water partition coefficient values (Pow). Amitriptyline had an IC50 of 1.26+/-0.29 mM, desipramine 75.99+/-14.40 mM, while lofepramine had an IC50 of 357.40+/-25.00 mM. Lignocaine had an IC50 of 85.73+/-18.30 mM. There was also a significant correlation between the IC50 values and the Pow values.

Amitriptyline↗
PubMed1999

Assessment of disorder in crystalline powders--a review of analytical techniques and their application.

The need to be able to measure amorphous contents in crystalline powders is now recognised. In this review, calorimetric and gravimetric methods are reviewed in a way that should alert workers in the field to the theoretical, and practical considerations which are important to understanding how best to study crystalline samples which contain low levels of amorphous material. It is shown that vapour sorption techniques are very powerful as long as serious consideration is given to the choice of environmental conditions and the exact experimental methodology. As the amount of published work in this field grows, it becomes increasingly necessary to describe experimental and data manipulation methods in great detail.

Calorimetry↗
PubMed1999

Acute toxicity profile of maprotiline in the rat.

The aim of the present study was to examine the toxic effects of single oral administrations of the antidepressant maprotiline at 150 mg/kg or 300 mg/kg using female Sprague-Dawley rats. Body-weight gain was significantly reduced in the group receiving 300 mg/kg on days 1-5 of the study (P<0.01). A significant reduction in food and water intake was observed on days 1 and 2 of the study (P<0.01) in the 300 mg/kg group and on day 1 in the 150 mg/kg group (P<0.05). There was a significant decrease in nocturnal home cage activity over the first five days of the study in the 300 mg/kg group (P<0.01). A significant hypothermic response was observed in both 150 and 300 mg/kg groups at 1, 2 and 4 hr after dosing (P<0.01), that had returned to control values within 8 hr following administration. This study demonstrates that a multi-parameter approach is appropriate for the investigation of high doses of antidepressants in rodents.

Animals↗
PubMed1998

Crystallization of bulk samples of partially amorphous spray-dried lactose.

The crystallization of partially amorphous spray-dried lactose was studied as a function of sample size. Crystallization occurred gradually over a period of 80 hr for a 95-g sample. The water content during crystallization was lower than that needed to cause crystallization if it had been distributed evenly throughout the bed, thus the absorbed water must have been unevenly distributed. The weight of the sample continued to change for days after crystallization was completed, because of the slow desorption of condensed water and the very slow formation of the hydrate form. Surprisingly, all samples with a weight between 42 and 95 g were found to take up the same mass (not percent) of water at the same time. This provides further evidence that the water was not evenly distributed throughout the sample. Water loss after this peak differed in the different weight samples, with the largest weights resulting in the lowest residual weight after 2 weeks. Only the sample of 22 g load had a different peak weight and a much lower weight loss after crystallization. This study provides detail of how partially amorphous bulk samples crystallize.

Calorimetry↗
PubMed1993

Identification of brain isoforms of the rat calcitonin receptor.

Two rat calcitonin receptor isoforms have been identified by cDNA cloning from a hypothalamic library. The clones, C1a and C1b, specified proteins of 478 and 515 amino acids, respectively. The clones were identical, except that the C1b sequence encoded a 37-amino acid insert in the second extracellular domain, which conferred altered ligand recognition. Compared to the C1a receptor, expressed C1b receptors exhibited decreased affinity for porcine CT, relative to salmon CT, and negligible affinity for human CT. Clone C1b mRNA was predominately expressed in the brain, whereas mRNA for the C1a clone was present in both brain and peripheral tissues. Both receptors were able to couple functionally to adenylate cyclase. Thus, clone C1b represents a novel brain isoform of the CT receptor with different affinity for CT analogs resulting from an altered second extracellular domain.

Adenylyl Cyclases↗