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Biomedical subjects

P H Redfern

Publications and source records attributed to P H Redfern.

At least 37 records · Page 2Linked to original sources
PubMed1985

The effect of antidepressant drugs on 24-hour rhythms of tryptophan metabolism in the rat.

The effect of three antidepressant drugs, imipramine hydrochloride, clomipramine hydrochloride and zimelidine dihydrochloride on plasma free and total TRY concentrations has been examined. The drugs were administered to male Wistar rats in the drinking water at a concentration of 200 micrograms ml-1 for up to 15 days. The effects of TRY concentration were complex and, after 2 days, inconsistent. After 14 days, the overall effect of imipramine was to lower free TRY levels and abolish 24-hr variation in free TRY concentration. Zimelidine and clomipramine tended to increase free TRY, particularly at 1300h so that the overall effect was to delay the peak in plasma-free TRY until later in the day. The possible significance of these findings to the mechanism of action of antidepressant drugs in clinical practice is discussed.

Administration, Oral↗
PubMed1983

The chronic effects of beta-adrenoreceptor blocking agents on transmitter overflow in the anococcygeus muscle of the rat.

1 The effect of chronic administration of three beta-adrenoreceptor blocking agents, propranolol, timolol and atenolol on transmitter release from sympathetic nerves has been investigated in the isolated anococcygeus muscle of the rat. 2 Oral treatment for 11 weeks with either propranolol (12 mg/kg/day), or timolol (1.2 mg/kg/day) but not atenolol (12 mg/kg/day) significantly increased the stimulation-induced overflow of radioactivity following preincubation of the tissue with 3H-NA. 3 No increase in end-organ sensitivity, as measured in terms of responsiveness to exogenous acetylcholine, tyramine or NA, was observed. 4 The ineffectiveness of atenolol compared to the other beta-adrenoreceptor blocking drugs may be related to the finding that, in acute experiments, atenolol inhibited tissue uptake of 3H-NA. 5 It is postulated that increased release of transmitter may be related to prolonged blockade of presynaptic beta-receptors and a resultant increase in presynaptic receptor sensitivity.

Adrenergic beta-Antagonists↗
PubMed1983

An investigation of the importance of the adrenal gland to the action of dopamine in the rat kidney.

1 In the rat, administration of dopamine is associated with diuresis, natriuresis and a decreased excretion of K+. The site of action of dopamine in mediating these responses has been investigated. 2 Urine volume, and urinary Na+, K+, Cl- and dopamine concentrations have been measured in adrenalectomized and sham-operated male Wist ar rats. 3 As expected, adrenalectomy decreased urine volume and increased Na+ and Cl- excretion; at the same time the amount of dopamine excreted fell, and K+ excretion did not change. 4 Administration of either 3% NaCl (20 ml/kg orally) or frusemide (100 mg/kg s.c.) significantly elevated dopamine excretion after adrenalectomy. 5 When dopamine, 1, 10 and 30 mg/kg (s.c.) was given to adrenalectomized rats, the diuresis and fall in K+ excretion seen in control animals was still present. No further natriuresis, over and above the already high urinary Na+ levels, was observed. 6 The results show that the three actions of dopamine in inducing diuresis and natriuresis, and decreasing K+ excretion, are clearly separable. 7 It is further argued that in mediating these effects the main site of action of dopamine is the kidney rather than the adrenal gland.

Adrenal Glands↗
PubMed1980

The effect of viloxazine on drug-induced inhibition of food intake in the rat.

In male Wistar rats trained to eat their normal daily dietary requirement in a restricted 2 h period, dose-dependent decreases in food consumption were produced by fenfluramine, tiflorex, mazindol and amphetamine. The antidepressant drug viloxazine (Vivalan) alone did not alter food intake significantly, nor did the drug prevent the inhibitory effects of either mazindol or amphetamine. However, complete prevention of the inhibitory effect of fenfluramine was achieved with 7.5 mg kg-1 viloxazine, while 40 mg kg-1 viloxazine similarly prevented the anorectic action of tiflorex. An interaction involving 5-hydroxytryptaminergic mechanisms is suggested, and since viloxazine given after fenfluramine or tiflorex produced no reversal of the inhibition of food intake, it is suggested that viloxazine prevents access of the anorectic agents to their site of action. The clinical significance of these interactions is discussed.

Amphetamine↗
PubMed1980

Factors affecting the release and excretion of dopamine in the rat.

The effects of inorganic salts and of diuretic agents on the excretion of dopamine (DA) were examined in the rat. Both types of treatment evoked significant increases in urinary DA excretion, urine volume and urinary sodium excretion. In the salt-treated animals a significant correlation was observed between DA excretion and urine volume, whereas after diuretic treatment there was better correlation between DA and urinary sodium excretion. The salt-treated animals showed a high correlation between administered chloride and DA excretion. Subcutaneous administration of DA produced a significant diuresis and an increase in sodium excretion. The mechanisms responsible for these responses are discussed with reference to the possibility that DA has a physiological role in the kidney.

Animals↗
PubMed1979

Surfactant ion-pair high-performance liquid chromatography of tryptophan and some of its metabolites in biological fluids.

A rapid, sensitive assay for tryptophan and some of its metabolites in urine, plasma and saliva has been developed using sodium dodecylsulphate as a pairing ion in a surfactant ion-pair high-performance liquid chromatography technique. The method is highly selective for tryptophan which is separated from its main indoleamine metabolites, 5-hydroxytryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, and from kynurenine. The usefulness of the assay has been demonstrated in plasma level and urinary excretion studies of orally administered tryptophan.

Biological Availability↗
PubMed1978

The mechanism of the hypothermic effect of amantadine in rats and mice.

Amantadine (25--100 mg kg-1, i.p.) given to rats at an ambient temperature of 4 degrees, or mice at 21 degrees, caused a marked fall in rectal temperature. Prior administration of pimozide (1--2 mg kg-1, s.c.) did not block hypothermia due to amantadine in rats or mice; in contrast, hypothermia due to apomorphine (2 mg kg-1, i.p.) and piribedil (10--40 mg kg-1, i.p.) in rats was blocked by pimozide pretreatment. Amphetamine (5 mg kg-1, i.p.) given 2 h after reserpine (2 mg kg-1, i.p.) caused a reversal of the hypothermic effect of reserpine in mice, but a reversal was not obtained with amantadine (50 mg kg-1, i.p.). Direct injection of amantadine (4--8 mg kg-1) into the cerebral ventricles (i.c.v.) of mice caused marked hypothermia which was not blocked by pimozide, but intravenous injection of the same dose of amantadine did not cause hypothermia. Rimantadine, a congener of amantadine but without anti-parkinsonian activity, also caused pimozide insensitive hypothermia in mice at doses of 50 mg kg-1, intraperitoneally or 2--4 mg kg-1, intracerebroventricularly. The main conclusion drawn from these results is that in causing hypothermia amantadine acts in the cns but not on dopamine receptors.

Amantadine↗
PubMed1977

Twenty-four hour rhythms in serum and brain indoleamine concentrations: tryptophan-5-hydroxylase and monoamine oxidase activity in the rat.

The relationship between the 24 h rhythm in 5-hydroxy-tryptamine (5HT) levels in rat brain, the availability of precursors of 5HT and the concentration of its major metabolite, 5-hydroxyindole acetic acid (5HIAA) has been investigated. Serum total and "free" tryptophan (TRY) levels and brain TRY levels all show a 24 h rhythm with highest concentrations in the middle of the dark phase i.e. 12 h displaced from that of the 5HT rhythm. No 24 h variation in either tryptophan-5-hydroxylase or monoamine oxidase activity was detected, nor did brain 5-hydroxytryptophan (5HTP) levels vary with clock hour. Changes in 5HIAA concentration paralleled those of 5Ht. The uptake of 14C-5HTP, 14C-TRY and 14C-5HT into homogenates of the septal region of rat brain did not display a circadian rhythm, although there was evidence that uptake of 14C-TRY in an isolated synaptosomal preparation from the same region was greater during the light phase, indicating the possibility that uptake of the precursor into the nerve ending may be, in part, responsible for the 24 h rhythm in brain 5HT. It is concluded that brain 5HT levels are independent of the serum or brain TRY concentrations measured. Since changes in 5HT with clock hour are paralleled by changes in 5HIAA, it also seems unlikely that the increase in brain 5HT during the light phase is caused by a decreased release of 5HT from nerve endings.

5-Hydroxytryptophan↗