Metaraminol Guanethidine

The noradrenaline normally contained in the storage granules can be partly or completely replaced by structurally related sympathomimetic amines, either by injection of the amine itself, or of suitable precursors such as a-methyl-DOPA or a-methyl-w-tyrosine. These amines can be depleted from the heart by guanethidine in the same way as the noradrenaline which they had replaced. a-Methylnoradrenaline [337] and metaraminol [338] are depleted less readily than noradrenaline from rabbit or rat hearts, whereas dopamine, octopamine and w-octopamine are depleted more readily than noradrenaline [339]. The more rapid depletion of these last three compounds was attributed to weaker binding in the storage granules [339], but could equally well be due to their greater susceptibility to destruction by monoamine oxidase, since both a-methyl-noradrenaline and metaraminol are resistant to attack by monoamine oxidase. 

Guanethidine and related drugs make adrenoceptors highly sensitive to metaraminol (2). 

The pressor effects of noradrenaline (norepinephrine), phenylephrine, and metaraminol can be increased in the presence of guanethidine. These drugs can also be used as eye drops, and in this situation their mydriatic effects are similarly enhanced and prolonged by guanethidine. 

Although vesicles bind either NA or ADR. the storage mechanism is not specific for these amines. Other related compounds can also be bound within medullary or neuronal vesicles. For example, L-metaraminol and p-tyramine can stoichiometrically replace the endogenous catecholamine, without affecting the ATP content of the storage vesicles. Many other amines will bind in a similar manner, e.g. guanethidine and 5-hydroxytryptamine. 

---