Biomedical subjects

G Weiner

Publications and source records attributed to G Weiner.

25 records · Page 2Linked to original sources

PubMed1979

Studies on SK&F 29661, an organ-specific inhibitor of phenylethanolamine N-methyltransferase.

SK&F 29661 is an effective, reversible inhibitor of both central nervous system and adrenal phenylethanolamine N-methyl-transferase in vitro; its Ki values in our standard assay systems were 6 X 10(-7) M (central nervous system) and 3 X 10(-7) M (adrenal), respectively. In vivo, the drug inhibited the conversion of [3H]norepinephrine to [3H]epinephrine in the rat adrenal gland and upon chronic administration decreased the endogenous adrenal epinephrine/norepinephrine ratio in both the rat and squirrel monkey. SK&F 29661 did not, however, reduce rat brain stem PNMT activity after systemic administration; subsequent radioautographic studies indicated that the compound did not enter the central nervous system, presumably because of its high polarity. This drug may be useful in defining the physiological importance of peripheral phenylethanolamine N-methyltransferase inhibition.

Adrenal Glands↗

PubMed1977

The effects of an inhibitor of phenylethanolamine N-methyltransferase upon stimulated adrenal catecholamine release and excretion in the rat.

SK&F 64139, an inhibitor of adrenal phenylethanolamine N-methyltransferase (PNMT), was found to significantly decrease 2-deoxy-D-glucose (2-DG) induced epinephrine excretion in the conscious rat under conditions where the former agent was administered chromically at 50 and 200 mg/kg/day over a 12-day period and 2-DG was administered after 3, 7 and 11 days of treatment. The reduced epinephrine output caused by SK&F 64139 in response to 2-DG was accompanied by an increased norepinephrine excretion pattern at 200 mg/kg/day of the compound. The reductions in epinephrine excretion were also associated with significant decreases in adrenal epinephrine and increases in the norepinephrine content.

Adrenal Glands↗

PubMed1977

The effect of phenylethanolamine n-methyltransferase concentration and species difference on the inhibitory potency of SK&F 64139.

We have found that the potency of SK&F 64139 in inhibiting rabbit adrenal phenylethanolamine N-methyltransferase (PNMT) is a function of protein concentration when high concentrations of the latter are employed. At lower enzyme levels, however, the degree of inhibition produced by the drug becomes independent of PNMT, allowing for the proper calculation of an inhibition constant. The Ki for the compound under these circumstances was 3 nM. Inhibitor dissociation constants within the same order of magnitude were subsequently obtained using the adrenal enzyme obtained from the rat, cow, dog, human and squirrel monkey. These data provide evidence that the PNMT receptor sites for SK&F 64139 do not differ substantially from species to species and suggest the general utility of this drug as an inhibitor of adrenal epinephrine biosynthesis.

Adrenal Glands↗

PubMed1973