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Biomedical subjects

S E Browne

Publications and source records attributed to S E Browne.

30 records · Page 2Linked to original sources
PubMed1994

Differential patterns of local cerebral glucose utilisation associated with rilmenidine- or B-HT 933-induced hypotension.

The anti-hypertensive drug, rilmenidine, has activity at both imidazoline-preferring receptors (IPRs) and alpha 2-adrenoceptors. However, available evidence suggests that its hypotensive effect is mediated via central IPRs. In the present study, the neuroanatomical regions involved in mediating the hypotensive response to rilmenidine were investigated using the [14C]2-deoxyglucose in vivo autoradiographic technique to map drug-induced changes in glucose utilisation within the CNS of conscious, spontaneously hypertensive rats (SHR). The cerebral metabolic effects of rilmenidine were compared with those of B-HT 933, a selective, alpha 2-adrenoceptor agonist with no selectivity for the IPR. Rilmenidine (1 mg/kg, s.c.) and B-HT 933 (2 mg/kg, s.c.) both elicited a moderate but significant hypotension (-24 +/- 2 and -18 +/- 5 mmHg, resp.) and bradycardia (-62 +/- 19.5 and -69 +/- 14 beats/min, resp.). [14C]2-deoxyglucose autoradiography, initiated after stabilisation of the drug-induced reduction in blood pressure, revealed significant reductions (P < 0.05) in local cerebral glucose utilisation (LCGU) in the intermediolateral cell column of the spinal cord, area postrema, ventrolateral medulla, nucleus tractus solitarius and cuneate nucleus of rilmenidine-treated rats. Rilmenidine did not significantly alter LCGU in a number of structures containing high densities of alpha 2-adrenoceptors such as nucleus accumbens, locus coeruleus, frontal cortex. No significant changes in glucose use were evident in any of the 26 CNS regions examined following B-HT 933 administration. These results provide evidence for the functional involvement of brainstem cardiovascular control centres in the central hypotensive effects of rilmenidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

AMPA receptor antagonists and local cerebral glucose utilization in the rat.

Local cerebral glucose utilization was examined using [14C]2-deoxyglucose autoradiography following systemic administration of the AMPA antagonists 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) and 6-(2-(1H-tetrazol-5-yl)ethyl)decahydroisoquinoline-3-carboxy lic acid (LY-293558) in conscious rats. Both NBQX (10, 30 and 100 mg/kg) and LY-293558 (10, 30 and 100 mg/kg) produced marked, anatomically widespread, dose-dependent reductions in glucose utilization throughout the brain. In none of the 50 regions investigated were elevations in glucose use observed at any dose of either agent. The reductions in glucose use were accompanied by sedation, suppression of spontaneous behaviour, and respiratory depression after NBQX (30 and 100 mg/kg) and LY-293558 (30 and 100 mg/kg) administration. The greatest reductions in glucose use after NBQX or LY-293558 occurred in primary auditory regions, limbic structures (particularly hippocampal regions and cingulate cortex), neocortex and some thalamic nuclei. However, a small number of regions were found to be insensitive to either NBQX or LY-293558, most notably the superior colliculus superficial layer which failed to display significant alterations in glucose use following any concentration of either AMPA antagonist. The anatomical pattern of altered glucose use was essentially similar following either agent although the cerebral cortex, thalamus and auditory regions were more sensitive to LY-293558 and subcortical regions more sensitive to NBQX. The anatomical pattern of glucose use alterations after AMPA receptor antagonists differs from that described previously for competitive and non-competitive NMDA receptor antagonists.

Animals↗
PubMed1993

Pharmacological modification of glutamate neurotoxicity in vivo.

The ability of five agents (dizocilpine [MK-801], 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline [NBQX], enadoline [CI-977], L-nitroarginine methyl ester [L-NAME] and BW 1003c87) with well defined, distinct pharmacological profiles and with established anti-ischemic efficacy, to modify neuronal damage has been examined in a simple in vivo model of glutamate excitotoxicity. Cortical lesions were produced in physiologically-monitored halothane-anesthetised rats by reverse dialysis of glutamate. The volume of the lesion was quantified histologically by image analysis of approximately 20 sections taken at 200 microm intervals throughout the lesion. The AMPA and NMDA receptor antagonists (NBQX and MK-801) and the inhibitor of nitric oxide synthase (L-NAME) significantly reduced the lesion volume by a similar extent (by approximately 30% from vehicle). Two agents (the kappa opioid agonist, CI-977 and the sodium channel blocker, BW 1003c87) which putatively inhibit the release of endogenous glutamate presynaptically, had dissimilar effects on lesion size. CI-977 failed to alter the amount of damage produced by exogenous glutamate, whereas BW 1003c87 reduced the lesion size by approximately 50%. Using this model, the neuroprotective effects of anti-ischemic drugs can be explored in vivo, uncomplicated in contrast to experimental ischemia by reduced oxygen delivery, drug effects on tissue blood flow and compromised energy generation. In consequence, additional mechanistic insight into anti-ischemic drug action in vivo can be obtained.

Amino Acid Oxidoreductases↗
PubMed1991

An investigation of the involvement of GABA in certain pharmacological effects of delta-9-tetrahydrocannabinol.

Experiments were performed with mice to determine whether doses of the benzodiazepine, flurazepam, or the GABA uptake inhibitor, NO-328, known to potentiate catalepsy induced by delta-9-tetrahydrocannabinol (THC), would also interact synergistically with THC in the production of certain other effects. No synergism was detected either in the production of antinociception (tail flick test) or in a test in which the ability of flurazepam to delay onset of clonic convulsions induced by intravenous infusion of pentylenetetrazole was compared in the presence and absence of THC or cannabidiol. The hypothermic effect of THC was unaffected by NO-328 but enhanced by flurazepam, albeit only at doses higher than those needed to potentiate THC-induced catalepsy. In vitro experiments with guinea pig ileum showed that the ability of THC to inhibit electrically evoked contractions was unaffected by delta-amino-n-valeric acid, a GABA(B) receptor antagonist, and that preparations rendered tolerant to GABA responded normally to THC. Contractions induced by GABA in unstimulated ileal longitudinal muscle were attenuated by THC. We conclude that there is little evidence from our data that any of the THC effects studied were GABA mediated.

Amino Acids↗