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P F Hunt

Publications and source records attributed to P F Hunt.

8 recordsLinked to original sources
PubMed1991

The dopamine D2 agonists RU 24213 and RU 24926 are also kappa-opioid receptor antagonists.

The di-(phenethyl)-amine derivatives, RU 24213 and RU 24926 are widely used as selective dopamine D2-receptor agonists. Binding studies now show that they also have affinity for the kappa-opioid receptor. Their affinity is not greatly reduced in the presence of NaCl/GTP, suggesting an antagonist action. This is confirmed for RU 24926, the more active of the two, using the field-stimulated rabbit vas-deferens. With respect to the mu-receptor, RU 24926 shows low binding affinity and also an antagonist effect. These results demonstrate kappa- as well as mu-antagonist activity in a novel chemical series. Moreover, since the kappa-receptor may regulate dopamine release, the results of experiments using these compounds as dopamine D2 agonists should be interpreted with caution.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

GABA release from mouse striatal neurons in primary culture as a test for the functional activity of N-methyl-D-aspartate (NMDA) antagonists.

N-Methyl-D-aspartate (NMDA)-induced release of [3H]GABA from mouse striatal neurons in primary culture has been evaluated as a screening method for demonstrating the functional activity of potential NMDA antagonists with respect to a cellular response. Antagonists were chosen for their specificity towards each of the three principal binding sites which have been characterised on the NMDA-receptor complex: the glutamate site, the ion-channel and in particular the glycine regulatory site where several novel halogenated derivatives of kynurenic acid have been tested. All the compounds were effective in blocking [3H]GABA release and their activity was related to their potency in displacing the binding of specific ligands for each of the three sites in rat cortex membrane preparations. This was confirmed by a correlation curve for the series of kynurenate derivatives (correlation coefficient r = 0.96). The specificity of these latter compounds for the glycine site was demonstrated by the addition of excess glycine which totally reversed their inhibition but not that of antagonists acting at the glutamate or ion-channel sites. Within the kynurenate series the 5,7-dichloro derivative was shown to be more active than the 7-chloro derivative, the most active glycine antagonist previously described. These results show that this is a simple and reliable system for demonstrating a functional effect of NMDA antagonists.

Animals↗
PubMed1976

Dichlorvos -- a 2-year inhalation carcinogenesis study in rats.

To determine the effects of dichlorvos vapour on the tumour incidence in rats, 5 week old Carworth Farm E strain rats weighing between 94 and 150 g were exposed to 0, 0.05, 0.5 and 5.0 mg/m3 in a 2-year inhalation study. The growth rate of all treated rats was depressed, particularly in the males. There was increased survival of the rats exposed to 5 mg/m3. There were no consistent differences in food intakes, organ weights, haematological or blood chemistry estimations, except in cholinesterase activites, amongst the various groups of rats. No compound-related differences were seen in acetylcholine and choline estimations carried out on a small number of female rats' brain tissues after two years' exposure. There were no gross or microscopical compound-related changes in the rats' tissues. Ultrastructural examination of the respiratory tissues of the rats from the control and 5 mg/m3 group showed no changes attributable to dichlorvos. The results of a relative risk analysis of the tumour data showed that no dose-related increase in tumour risk was established for rats of either sex. These data confirm the results of earlier st.udies supporting the safety of insecticidal uses of dichlorvos.

Animals↗
PubMed1976

Comparative action of fenfluramine on the uptake and release of serotonin and dopamine.

The anorectic agent, fenfluramine, proves to be a good inhibitor of serotonin uptake in vitro, in synaptosomes from rat whole brain (IC50 = 8.5 +/- 0.6 X 10(-7) M). After administration in vivo, its inhibitory activity in vitro equals that of chlorimipramine and in contrast to the latter, its effect is of long duration. Fenfluramine is also effective in promoting the release of serotonin from pre-loaded synaptosomes. In comparison, the structurally related compound, amphetamine, has little activity with respect to these serotonin mechanisms. It is, however, active both in inhibiting the uptake of dopamine and in promoting its release, whereas fenfluramine is inactive. The implication of these mechanisms in the serotonin-depleting capacity as well as in the anorectic activity of fenfluramine is discussed.

Animals↗
PubMedDate not supplied

The carcinogenic response in mice to the topical application of propane sultone to the skin.

The carcinogenic effects of limited and repeated skin applications of propane sultone were investigated in three strains of mice, CF1, C3H and CBah (a hairless strain). Propane sultone was shown to be carcinogenic when given as a single application of a 25% w/v solution in toluene and also following twice weekly application of a 2.5% w/v solution for up to 58 weeks. More limited exposure to 2.5% w/v solutions of propane sultone resulted in a few skin tumours, although the incidences were not statistically significant. Most neoplasms were papillomas or carcinomas, although a small number of mesenchymal tumours of dermal origin also developed. No skin neoplasms were found in any control mice. The skin application of propane sultone was associated with a statistically significant increase in the incidence of systematic neoplasia in CFl and C3H mice. The exposed CFl mice had a higher incidence of neoplasms of lymphoreticular and lung origin, while female C3H mice showed a higher incidence of mammary gland and uterine tumours. In mice exposed to beta-propiolactone as a positive control, neoplasms developed at the site of application but, there was no evidence of increased systemic neoplasis in contrast to the findings with ptopane sultone.

Animals↗