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Biomedical subjects

R W Fuller

Publications and source records attributed to R W Fuller.

At least 361 records · Page 20Linked to original sources
PubMed1981

Comparative effects of amantadine and amfonelic acid on dopamine metabolism in rat brain.

Amantadine (50 and 100 mg/kg IP) did not change basal levels of DOPAC (3,4-dihydroxyphenylacetic acid) or HVA (homovanillic acid) in rat brain and did not alter the increase in DOPAC levels resulting from dopamine receptor blockade by spiperone. The increase in HVA levels produced by spiperone was significantly, but only slightly, enhanced by amantadine at these doses. In contrast, amfonelic acid at a dose of 5 mg/kg increased DOPAC and HVA levels and enhanced several-fold the spiperone-induced elevation of DOPAC and HVA levels. Amfonelic acid at at 2.5 mg/kg dose enhanced the turnover of dopamine (measured by the decline in dopamine concentration after inhibition of tyrosine hydroxylation with alpha-methylytyrosine) in spiperone-treated rats, whereas amantadine (100 mg/kg) had a smaller and not statistically significant effect. Neither compound affected significantly dopamine levels in a alpha-methyltyrosine-treated rats not given spiperone. Although amantadine has been observed by earlier workers to enhance the stimulated release of dopamine, it does not appear to act in a manner similar too amfonelic acid.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Cyclic urea nucleosides. Cytidine deaminase activity as a function of aglycon ring size.

Five beta-D-ribofuranosyl cyclic urea nucleosides (14-18), ranging in ring size from five to eight membered, were synthesized and evaluated as cytidine deaminase (CDA) inhibitors. The precursor protected nucleosides (9-13) were prepared by a condensation procedure utilizing persilylated ureas with a halo sugar under the specific catalytic activity of a HgO/HgBr2 mixture which provided exclusively the beta-anomers. Catalytic hydrogenation of known 1-(2,3,5-tri-O-benzoyl-beta-ribofuranosyl)-1,2-dihydropyrimidin-2-one (19) afforded nucleoside 10 identical with that obtained by the mercury-catalyzed condensation procedure. CDA activity varies significantly with the ring size of the urea aglycon the reaches its maximum level for the seven-membered analogues 16 and 17. The unexpected high potency of nucleoside 17 (Ki = 2.5 X 10(-8) M, human liver enzyme) is reported. This compound represents the most potent inhibitor of human liver CDA yet discovered.

Animals↗
PubMed1981

Lowering of blood pressure by direct- and indirect-acting serotonin agonists in spontaneously hypertensive rats.

1-(m-Trifluoromethylphenyl)piperazine, a serotonin agonist, lowered blood pressure in spontaneously hypertensive rats (SHR) at doses of 2 to 10 mg/kg s.c. A structurally related compound lacking serotonin agonist activity, 4-(m-trifluoromethylphenyl)piperidine, was ineffective. Quipazine, another serotonin agonist, lowered blood pressure in SHR at doses of 0.1 to 2 mg/kg s.c. Fenfluramine, a serotonin-releasing drug, lowered blood pressure in SHR at doses of 2 and 5 mg/kg s.c. Metergoline (3 mg/kg s.c.), a serotonin antagonist, elevated blood pressure and prevented the decrease by all of the above agents. These findings are consistent with the view that enhancement of central serotonergic function lowers blood pressure in SHR.

Animals↗
PubMed1981

Comparison of o-octopamine and related phenylethanolamines as substrates for norepinephrine N-methyltransferase.

o-Octopamine was a substrate for rabbit adrenal norepinephrine N-methyltransferase with lower affinity than the position isomers m-octopamine and p-octopamine. The order of substrate affinity for monochloro or monohydroxy phenylethanolamines was para greater than meta greater than ortho. With phenylethanolamine and ring-hydroxylated phenylethanolamines, primary amines were better substrates than were N-methyl secondary amines. N-Methylation might be a metabolic pathway for o-octopamine, reported to occur in mammalian tissues.

Adrenal Glands↗
PubMed1981

Sympathetic noradrenergic innervation of guinea-pig liver: histofluorescence and pharmacological studies.

Norepinephrine concentration was higher in guinea-pig liver than in rat or mouse liver and evidence was obtained that the norepinephrine was present within nerves. In guinea pigs, norepinephrine in liver was depleted by reserpine, 6-hydroxydopamine and metaraminol. The depletion by 6-hydroxydopamine and metaraminol was antagonized by prior treatment with desipramine, an inhibitor of uptake into norepinephrine neurons. Guinea-pig liver concentrated metaraminol to a greater extent than did rat liver; the concentration of metaraminol was lowered by desipramine pretreatment and, within three tissues of the guinea pig (heart greater than liver greater than muscle), paralleled the concentration of endogenous norepinephrine. These findings constitute pharmacological evidence for noradrenergic innervation of guinea-pig liver to a greater extent than in other species. Histofluorescence studies confirmed the existence of norepinephrine-containing nerve terminals in guinea-pig liver. Norepinephrine-containing varicosities were seen adjacent to the hepatic artery, portal vein and bile duct in the portal spaces and adjacent to sinusoid capillaries and hepatocytes in the liver parenchyma. These findings strengthen the evidence for sympathetic innervation of liver and suggest the guinea pig as a useful species in exploring physiological roles of noradrenergic innervation of liver.

Animals↗
PubMed1981

Elevation of epinephrine concentration in rat brain by LY51641, a selective inhibitor of type A monoamine oxidase.

LY51641, N-[2-(o-chlorophenoxy)ethyl]cyclopropylamine hydrochloride, selectively inhibited type A monoamine oxidase (MAO) (measured with 10 microM 14C-serotonin as substrate) without inhibiting type B MAO (measured with 12.5 microM 14C-phenylethylamine as substrate) in rat brain. The inhibition of type A MAO was accompanied by an increase in epinephrine concentration in hypothalamus. Although the absolute concentration of epinephrine in rat hypothalamus is low relative to norepinephrine and dopamine, the percentage increase in epinephrine after LY51641 was greater than the percentage increase in dopamine or norepinephrine. The inhibition of type A MAO activity and increase in hypothalamic epinephrine concentration following a single 30 mg/kg dose of LY51641 persisted for at least 10 days. Both effects were seen at doses as low as 0.03 mg/kg of LY51641. A 0.2 mg/kg dose of LY51641 given daily for 5 days retained selectivity in inhibiting type A MAO and increased epinephrine concentration. Two analogs of LY51641 of differing selectivity elevated epinephrine concentration to a degree related to percentage inhibition of type A MAO, and the effect of LY51641 was antagonized by pretreatment with harmaline, a short-acting reversible inhibitor of type A MAO. These findings support earlier evidence that in rat hypothalamus, epinephrine oxidation occurs by type A not type B MAO.

Animals↗
PubMed1981

Diffuse interstitial renal tuberculosis--an unusual cause of renal failure.

Three immigrant patients are described with diffuse interstitial renal tuberculosis. Two had associated pulmonary tuberculosis and the third had tuberculous peritonitis. Excretion urography gave no clue to the diagnosis. At the time of diagnosis by renal biopsy two patients had severe chronic renal failure. In one, renal impairment had progressed during the course of anti-tuberculous treatment. The third patient showed marked fluctuations in renal function, and improvement appeared to relate to concomitant corticosteroid therapy. The importance of this particular form of renal tuberculosis has not previously been emphasized.

Adult↗
PubMed1980

Long-lasting depletion of striatal dopamine by a single injection of amphetamine in iprindole-treated rats.

A single injection of amphetamine given to rats treated concurrently with iprindole so that they could not metabolize the amphetamine by para-hydroxylation resulted in a decrease in the concentration of striatal dopamine 1 week later. The decrease was antagonized by amfonelic acid, an inhibitor of uptake into dopamine neurons. The long-lasting depletion of cerebral dopamine by amphetamine may be analogous to the depletion of cerebral serotonin by halogenated derivatives of amphetamine.

Amphetamine↗