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Biomedical subjects

H D Snoddy

Publications and source records attributed to H D Snoddy.

At least 91 records · Page 5Linked to original sources
PubMed1975

Norepinephrine N-methyltransferase inhibition by benzamidines, phenylacetamidines, benzylguanidines, and phenylethylguanidines.

Norepinephrine N-methyltransferase (NMT) from rabbit adrenal glands was inhibited by benzylamine and phenethylamine analogs in which the nitrogen was replaced by an amidino or guanidino group. Mono and dichloro derivatives of benzamidines, phenylacetamidines, benzylguanidines, and phenethylguanidines were studied. The two most potent NMT inhibitors among the compounds examined were 2,3-dichlorobenzamidine and 3,4-dichlorophenylacetamidine, with pI50 values of 5.55 and 5.36, respectively. These inhibitors were reversible and were competitive with norepinephrine as the variable substrate. They inhibited NMT from human, rat, and bovine adrenal glands but were slightly less effective against those enzymes than against the rabbit adrenal enzyme. In exercised rats, 2, 3-dichlorobenzamidine had no significant effect on adrenal catecholamine levels. 3,4-Dichlorophenylacetamidine slightly reduced epinephrine levels in the adrenal glands of exercised rats, but the effect may have been due to release rather than inhibition of synthesis, since heart norepinephrine levels were also reduced significantly by that agent (which is from a chemical series known to release catecholamines). Thus, whereas these compounds are reasonably potent inhibitors of NMT in vitro, they apparently are not effective in blocking enzyme activity in vivo.

Acetamides↗
PubMed1975

Potentiation of the L-5-hydroxytryptophan-induced elevation of plasma corticosterone levels in rats by a specific inhibitor of serotonin uptake.

The ability of L-5-hydroxytryptophan (L-5HTP), a serotonin precursor, to elevate plasma levels of corticosterone in rats was confirmed. Pretreatment of the rats with 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenyl-propylamine hydrochloride (Lilly 110140) markedly enhanced the elevation of corticosterone levels by L-5HTP. Since Lilly 110140 is a specific inhibitor of serotonin uptake, these results support the hypothesis that L-5HTP elevates corticosterone by enhancing neurotransmission through a serotoninergic pathway influencing ACTH release.

5-Hydroxytryptophan↗
PubMed1975

Blockade of amine depletion by nisoxetine in comparison to other uptake inhibitors.

Nisoxetine, 3-(o-methoxyphenoxy)-3-phenyl-N-methyl-propyl-amine, is a new inhibitor of norepinephrine uptake. Nisoxetine antagonized 6-hydroxydopamine-induced depletion of norepinephrine in mouse heart with an ED50 of 0.9 mg/kg but had no effect on p-chloroamphetamine-induced depletion of serotonin in mouse brain at doses up to 32 mg/kg. Using the antagonism of these depleting agents to estimate inhibition of uptake into noradrenergic and serotoninergic neurons, we compared nisoxetine to several known amine uptake inhibitors. The order of effectiveness in antagonizing 6-hydroxydopamine action was protriptyline greater than desmethylimipramine greater than EXP 561 greater than nisoxetine greater than nortriptyline greater than chlorpheniramine greater than desmethylchlorimipramine greater than imipramine greater than doxepin greater than amitriptyline greater than chlorimipramine, with fluoxetine and its N-demethylated metabolite (103947) having no effect. In blocking p-chloroamphetamine, the order of effectiveness was EXP 561 greater than fluoxetine greater than 103947 greater than chlorpheniramine greater than chlorimipramine, with desmethylchlorimipramine, protriptyline, and nortriptyline having marginal effects and nisoxetine and the other drugs no effect at the highest dose tested, 32 mg/kg. Nisoxetine is thus one of the more potent and specific inhibitors of norepinephrine uptake, differing remarkably from fluoxetine to which it is related structurally.

Amines↗