Edwin A. Risley

Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs

Summary A method is presented for measuring the edema induced by injection of 0.05 ml of 1% solution of carrageenin, an extract of Chondrus, into the plantar tissues of the hind paw of the rat. Peak edema develops within the first 3 to 4 hours, and is inhibited by pretreatment of the animals by single oral doses of antiinflammatory agents, steroid or non-steroid. Log dose responses to drugs are linear and parallel, and yield potency ratios with relatively narrow confidence limits. The potency ratios obtained for aspirin, phenylbutazone and hydrocortisone are fairly close to the ratios of their respective daily doses in the treatment of rheumatic disease. A potent antihistaminic-antiserotonin compound, cyproheptadine, is without effect on carrageenin-induced edema.

CHARACTERIZATION OF THE BINDING OF [3H]MUSCIMOL, A POTENT γ‐AMINOBUTYRIC ACID AGONIST, TO RAT BRAIN SYNAPTOSOMAL MEMBRANES USING A FILTRATION ASSAY

Abstract— The binding of [3H]muscimol, a potent GABA agonist, to crude synaptic membranes prepared from rat brain was studied using a filtration method to isolate membrane‐bound ligand. Specific binding was found to be saturable and occurred to two binding sites of Kd5 5 and 30 nm. Binding was Na+‐independent and enhanced by both freezing and Triton treatment. Regional and subcellular distribution studies and pharmacological characterization of specific [3H]muscimol binding are consistent with binding to the synaptic GABA receptor.

Enhancement of the binding of 3H-diazepam to rat brain membranes in vitro by SQ 20009, a novel anxiolytic, γ-aminobutyric acid (GABA) and muscimol

Abstract SQ 20009, a compound with anxiolytic-like activity, was found to cause an enhancement of the binding of 3 H-diazepam to rat brain membranes in a concentration-dependent manner with inhibition of binding occuring at 10 −4 M. Both GABA and the GABA agonist, muscimol, were also found to enhance 3 H-diazepam binding while the GABA antagonist (+)-bicuculline decreased binding. The effects of SQ 20009, the GABA agonists and (+)-bicuculline were reflected as a change in the affinity rather than number of binding sites. The effects of SQ 20009 and GABA and muscimol are discussed in terms of an interaction with an endogenous diazepam-like factor.

Interaction of taurine and β-alanine with central nervous system neurotransmitter receptors

Taurine, a weak β-adrenergic agonist in rat pineal cultures, causes a 32% increase in the binding of the β-adrenergic antagonist 3H-dihydroalprenolol to rat brain membranes at a concentration of 100 mM. No significant effect was seen at 10 mM however. The amino acid is also effective in displacing 3H-diazepam (Ki, 32.8 mM) and 3H-muscimol (Ki, 32.4 μM), ligands for the benzodiazephine and GABA receptor, respectively. β-Alanine, a taurine analog, is more effective in displacing 3H-diazepam (Ki, 13.8 mM) and 3H-muscimol (Ki, 9 μM) but shows no significant enhancement of 3H-dihydroalprenolol binding. While endogenous taurine levels in brain are in the millimolar range, the physiological significance of these observations remains to be determined.

Comparison of central gastric antisecretory effects of desmethylimipramine, doxepin and pirenzepine in rats

SummaryCertain tricyclic drugs, some of which are primarily used clinically as antidepressants, have been shown to act as gastric antisecretory agents. The anatomical site(s) and mechanism(s) of action of these agents is, however, in most cases unclear. In this study, we found that desmethylimipramine (DMI) was approximately 28 times more potent in inhibiting gastric acid secretion when administered intracerebroventricularly (i.c.) than when administered intravenously (i.v.) in pylorus-ligated rats, which is indicative of a site of action in the central nervous system. Qualitatively similar results were obtained with pirenzepine where the i.c./i.v. potency ratio was 8. Doxepin also preferentially inhibited acid secretion when given i.c. at low but not at high doses. Atropine and chlorpromazine were equipotent antisecretory agents by both routes of administration. Doxepin and DMI but not pirenzepine were effective inhibitors of brain stem norepinephrine uptake in vitro thus making this an unlikely common mechanism to explain the central actions of these compounds.

Adrenal cortical activity in urine of horses.

Summary The presence of cortin-like activity in extracts of horse urine has been confirmed. It is estimated that the concentration of this active material is approximately the same in urine of normal horses and normal humans. There is some indication that urinary cortin-like activity is increased in pregnancy.