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R W Kerwin

Publications and source records attributed to R W Kerwin.

11 recordsLinked to original sources
PubMed1992

Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia.

According to the dopamine hypothesis of schizophrenia, D2 receptor blockade is essential for a drug to have antipsychotic potency, and antipsychotic potency and D2 blockade are linearly related in vitro. To test this assumption in vivo, we have compared clinical response with central D2 dopamine receptor availability measured by 123I-iodobenzamide single photon emission tomography in two groups of schizophrenic patients. 6 patients were on typical antipsychotic drugs and 10 were on the atypical antipsychotic clozapine, including 2 patients from the first group. The patients on typical antipsychotics showed poor therapeutic response despite D2 receptor blockade. Significant clinical improvement occurred in all patients on clozapine, but at a lower level of D2 blockade by the drug. These findings suggest a more complex relation between D2 blockade and clinical efficacy than was previously thought.

Adult↗
PubMed1992

A developmental perspective on the pathology and neurochemistry of the temporal lobe in schizophrenia.

Neuropathological, neuroimaging, clinical and epidemiological evidence suggests that many cases of schizophrenia are developmental in origin. Dysplastic changes in the medial temporal lobes appear to be of particular importance. However, research implicating a neurodevelopmental origin for schizophrenia has proceeded largely in isolation from knowledge concerning the neurochemistry of the disorder. This paper attempts to integrate these disparate lines of research, and examines the role of trophic mechanisms in the formation of the hippocampus. Those neurotransmitters which have been most consistently found to be abnormal in the temporal lobes of schizophrenics (excitatory amino acids and CCK), are involved in the control of hippocampal development. We suggest that these neurotransmitter findings are the residue of abnormalities in their role as trophic factors in foetal or neonatal life, and that the latter contribute to the developmental aberrations considered fundamental to schizophrenia.

Adult↗
PubMed1992

Clozapine.

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Ambulatory Care↗
PubMed1979

Specific stimulating effect of glycine on 3H-dopamine efflux from substantia nigra slices of the rat.

The effect of glycine was studied on the efflux of tritium-labelled dopamine, 5-HT and GABA from small slices of rat substantia nigra in vitro. A depolarising stimulus (50 mM KCl) stimulated the efflux of 3H-5HT, 3H-dopamine and 3H-GABA in a calcium-dependent fashion. Glycine (50 and 100 micromoles) stimulated the spontaneous efflux of 3H-dopamine but not that of 3H-5HT or 3H-GABA. Taurine, GABA and beta-alanine, all at 100 micromoles, had no effect on release of radioactivity after prelabelling nigral slices with 3H-dopamine. In keeping with a transmitter role for glycine at this site, 3H-glycine was taken up by small slices of rat substantia nigra by both high affinity (Km = 2.4 micromoles) and low affinity systems (Km = 5.96 mM). However 50 mM KCl was without effect on the efflux of radioactivity from nigral slices prelabelled with 3H-glycine.

Alanine↗
PubMed1979

Thyrotrophin releasing hormone stimulates release of [3H]-dopamine from slices of rat nucleus accumbens in vitro.

Thyrotrophin releasing hormone (TRH) (25 to 100 microM) was found to stimulate the efflux of [3Hu-dopamine from small slices of rat nucleus accumbens, but not from similar slices of rat caudate nucleus. Uptake inhibition was not responsible for this action, since at 10 and 50 microM TRH had no effect on the ability of small slices of nucleus accumbens to accumulate radioactivity when incubated with 10(-7) M [3H]-dopamine. In addition the hormone had no effect on basal or dopamine-stimulated adenylate cyclase, nor did it displace [3H]-spiperone binding, in membrane preparations from nucleus accumbens.

Adenylyl Cyclases↗
PubMed1979

Role of taurine as a possible transmitter in the thermoregulatory pathways of the rat.

Taurine (10 and 20 micrograms) injected unilaterally into the lateral ventricle of rats caused an increase in core temperature. Bilateral injection of taurine 2.5 and 5 micrograms into the preoptic region of the anterior hypothalamus induced a dose-related hyperthermia: higher doses (10 micrograms) caused hypothermia. Intrahypothalamically taurine-induced hyperthermia was blocked by prior injection of strychnine hydrochloride (5 and 15 micrograms); doses which alone had no effect on core temperature. Of the other inhibitory amino acids injected intrahypothalamically hypotaurine also induced a hyperthermia. GABA (10 micrograms) caused hypothermia; glycine (10 micrograms) had no effect. Potassium (50 mM) stimulated release of radioactivity from superfused slices of anterior hypothalamus prelabelled with [3H]taurine in a calcium-dependent manner. A high affinity uptake mechanism with a Km of 8.5 microM was demonstrated with [3H]taurine into slices of anterior hypothalamus. Taurine may have a neurotransmitter role in the anterior hypothalamus but whether the body temperature effects represent physiological or pharmacological events remains to be established.

Animals↗