ON THE MECHANISM OF HEART NOREPINEPHRINE DEPLETION BY TYRAMINE, GUANETHIDINE AND RESERPINE

¹ The Wellcome Research Laboratories, Burroughs Wellcome & Co. (U.S.A.) Inc., Tuckahoe, New York

When adequate levels of tyramine are maintained in the heart for a prolonged period (4 hr), this amine produces an almost complete depletion of heart norepinephrine. The results indicate that this depletion is due to a rapid decrease of norepinephrine from an easily releasable pool and then a slower release from a second pool, probably in equilibrium with the first.

The administration of B.W. 392C60, a compound which produces an adrenergic neurone blockade, prevents norepinephrine depletion caused by guanethidine, slows the depletion caused by reserpine but does not affect that elicited by tyramine.

The possibility is suggested that tyramine and guanethidine act on different stores of norepinephrine which are in equilibrium so that the depletion of one ultimately leads to the depletion of the other.

Results are presented which show that the effect of monoamine oxidase inhibitors and adrenergic neurone blocking agents on the depletion of norepinephrine by guanethidine, reserpine and tyramine is the same. This finding suggests a similar mechanism for the hypotensive action of monoamine oxidase inhibitors and adrenergic neurone blocking drugs.