Pharmacological properties of centrally administered ouabain and their modification by other drugs

Abstract

Summary1. Ouabain given by intracerebroventricular injection to mice in small doses (0-1-04 jg) produced a dose related depression of central nervous activity, characterized by a reduction in spontaneous locomotor activity, hypothermia, catalepsy and ptosis, lowered body posture and lack of response to external stimuli. Doses above 0 4 ,ug were excitatory, convulsant and lethal. 2. The depressant effects could be antagonized by (+)-amphetamine, desmethylimipramine, dibutyryl cyclic 3'5'-adenosine monophosphate and caffeine. 3. The MAO inhibitor nialamide produced only a small antagonism of ouabain, resulting in a greater rate of recovery from the depressant effects of ouabain. 4. The depressant effects were associated with a marked elevation of wholebrain dopamine levels with little change in noradrenaline or 5-hydroxytryptamine.5. The dopamine-3-hydroxylase inhibitor sodium diethyldithiocarbamate, administered by intracerebroventricular injection, produced effects qualitatively similar to those seen after ouabain.6. An interference with central transmitter function is postulated as a possible r.'ode of action of intracerebroventricularly injected ouabain.

THERMOREGULATORY EFFECTS OF N6‐2′‐O‐DIBUTYRYL ADENOSINE 3′,5′‐MONOPHOSPHATE IN THE RESTRAINED MOUSE

“…Biphasic (Varagic & Beleslin, 1973;Clark, Cumby & Davis, 1974) may be a consequence of the nucleotide reaching more than one thermoregulatory site in the brain. Doggett & Spencer (1971) found db cyclic AMP (25 jg i.c.v.) was without effect on body temperature in the mouse.…”

“…(Duff, Cranston & Luff, 1972;Philip-Dormston & Siegert, 1975). Biphasic Doggett & Spencer (1971) found db cyclic AMP (25 jg i.c.v.) was without effect on body temperature in the mouse.…”

The hyperthermic effect of intracerebroventricular cholera enterotoxin in the unanaesthetized cat

“…into brain sites in which bacterial endotoxin and prostaglandin E1 caused fever (Lipton & Fossler, 1974). Dibutyryl cyclic AMP has been reported to antagonize ouabain-and reserpine-induced hypothermia in the mouse (Doggett & Spencer, 1971.…”

The Pharmacology of Sedative/Hypnotics, Alcohol, and Anesthetics: Sites and Mechanisms of Action

“…KRNJEVIC (1975) cites a wealth of data generally consistent with this postulate. He leans heavily on the observation that 2,4-DNP and uncoupIers of oxidative phosphorylation, of which barbiturates are one of the classic agents (BRODY andBAIN, 1951, 1954;BRODY, 1955), depress excitability of cortical neurons (DOGGETT et aI., 1970;DOGGETT and SPENCER, 1971;GODFRAIND et aI., 1970GODFRAIND et aI., , 1971). This depression is associated with an increase in K + permeability.…”