Pressor amines

Using the rat as a test object, the authors found that of a number of aminelike and other pressor compounds only one, phenylethylamine, had a prolonged action (5 to 30 minutes) on blood pressure (Table III). Of the others renin had only a relatively long action (5 minutes or less), while isoamylamine, tyramine, epinine, arterenol, hypertensin, casein hydrolyzate, epinephrine, and tryptamine had only a short action (2 minutes or less). Phenylethylamine therefore may be an example of either (1) or (3). This was an unexpected result, and suggests further the importance of certain amine pressor agents. DOPA, although not an amine, also had a prolonged action. 

Korn A, Wagner B, Moritz E, Dingemanse J. T3n amine pressor sensitivity in healthy subjects during combined treatment with moclobemide and selegiline. EurJ Clin Pharmacol (1996) 49, 273-8. 

Hyperthyroid patients Use tranylcypromine and isocarboxazid cautiously because of increased sensitivity to pressor amines. 

There have been reports of excessive hypotension and paradoxical pressor effects following intravenous administration of labetalol. These latter effects may be due to a labetalol-induced blockade of neuronal amine uptake, which increases the concentrations of norepinephrine in the vicinity of its receptors. 

Mechanism of Action A sympathomimetic amine that produces CNS and respiratory stimulation, mydriasis, bronchodilation, a pressor response, and contraction of the urinary sphincter Directly effects alpha and beta receptor sites in peripheral system. Enhancesreleaseof norepinephrine by blocking reuptake, inhibiting monoamine oxidase. Therapeutic Effect Increases motor activity, mental alertness decreases drowsiness, fatigue. 

It antagonises the vasoconstrictor and pressor effect of 5-HT as well as the action of the amine on a variety of extravascular smooth muscles. 

Tailor SAN, Shulman Kl, Walker SE, et al. Hypertensive episode associated with phenelzine and tap beer —a reanalysis of the role of pressor amines in beer. J Clin Psychopharmacol 1994 14 5-14. 

McCabe B. Dietary tyramine and other pressor amines in MAOl regimens a review. J Am Diet Assoc 1986 76 1059-1064. 

Tricyclic antidepressants potentiate the pressor effects of directly acting sympathomimetic amines, such as adrenaline (epinephrine) or noradrenaline (norepinephrine), to cause hypertension. Small amounts of these, such as may be present in local anaesthetic solutions, can be dangerous. Tricyclic antidepressants will inhibit the antihypertensive effects of the older anti hypertensive drugs, such as adrenergic neurone-blocking agents, e.g. guanethidine, a-methyl-DOPA, and clonidine. 

Of the three peptides, hypertensin is the most clearly understood, resulting as it does from the enzymatic action of renin on a specific substrate. It has already been discussed in that connection. Hypertensin is, however, considered separately, for we are not certain that renin (being impure) produces only a single effector substance (nor are we certain that hypertensin is pure). It is not known whether hypertensin is broken down into simpler effector components (such as pressor amines) by specific enzymatic action in smooth muscle or whether the peptide as itself acts upon arterioles. The composite result, however, fulfills the requirements we have set for the Hochdruckstoff the duration of action is much shorter than that of renin, but longer than epinephrine,... 

In spite of the lack of specificity of the method, it is obvious that amines which give a color by Richter s method (48) are usually increased in chronic hypertension, especially in the more severe forms. Because the more highly active phenolic amines are not measured by this method, and others might be present in too small amounts to measure, these results may be taken as a manifestation of a general disturbance of amino acid metabolism in chronic hypertension which may include the formation of pressor amines it does not prove their presence. 

Table II. Action of "Natural Pressor Amines on Various Circulatory Functions...

Four substances have been described as having pressor effects, which are probably amines or aminelike. Urosympathin, described by Holtz, Credner, and Kronberg (34), is a substance found in normal urine in amounts per day, giving a pressor response equal to 2 to 3 mg. of hydroxytyramine or 100 to 150 micrograms of epinephrine or arterenol. In cases of essential hypertension the amount is said to be increased three- to fourfold. Because its action was intensified by cocaine and lessened by ergotoxin and yohimbine, they believed that it represented a mixture of hydroxytyramine, epinephrine, and arterenol. The material was recovered by lead acetate precipitation of urine with subsequent acid hydrolysis. 

A crude pressor substance was obtained from the anaerobic autolysis of renal tissue by Victor et al. (65), which was inactivated by tyrosinase (53) and amine oxidase. It probably contained isoamylamine, phenylethylamine, and tyramine (17) released by proteolytic enzymes. Pressor substances were not formed or were destroyed under conditions of aerobiasis. It is difficult to apply these results to in vivo pathological states except under extreme anoxia and necrosis of renal tissue. 

Before leaving the matter of amines, we should examine some of the known simpler ones for their effects upon the circulation, especially as to cardiac action and duration of pressor response. The former is noteworthy, as its absence is a necessary prerequisite of the Hochdruckstoff. Presumably an extended vasospastic action should also be a prerequisite. Prolonged action can be produced in at least four ways (1) by some property inherent in the structure of the molecule of the pressor agent which prevents its rapid destruction in situ or in blood (2) by slow liberation of an effector substance from a larger, more complex molecule or system (3) by inhibition of the action of an enzyme system which inactivates some naturally occurring pressor agent and (4) by continuous production from parent sources. Clear-cut examples are not evident at present, although... 

In order to integrate further some of the various reactions mentioned, and to detect its presence by other methods, the vessels of the rat s mesoappendix were employed as a test object (Chambers-Zweifach preparation, 12). A good correlation between the presence of a vasoexcitor material-like substance in the extracts and the presence of hypertension was found. When the whole rat was used for assay, a much cruder index, sizable quantities of active pressor material were isolated from the blood only of those patients showing at least a degree of renal impairment (lessened ability to concentrate urine, etc.). In general it may be stated unequivocally that patients with severe hypertension have in their arterial blood extractable substances which are pressor for the rat there are less or undemonstrable amounts in blood of less severe or neurogenic hypertensive patients there is little or none in blood of normotensive subjects a vasoexcitor material-like activity is exerted by blood from most hypertensive patients adenyl compounds, having a depressor action, present in extracts of blood are less prevalent in those from hypertensive patients the active rat pressor material (pherentasin) is probably aminelike in nature, is not a protein, but may be a simple peptide or an amine. 

Table IV. Pressor and Amine Oxidase Ratios of Naturally Occurring Amines...

Urohypertensin (1) was isolated from urine many years ago, and resembles in some respects Lockett s base A, except that it was not, like base A, precipitated with mercuric chloride. Bain (4) thought that isoamylamine, which he found in human urine, was urohypertensin. Lockett was unable to find isoamylamine in urine, although von Euler and Sjostrand (22) have stated that it is present in decreased amounts in essential hypertension. These pressor bases are worth further study, especially their relation to amines. 

Many other unidentified pressor materials have been isolated from organs and fluids (see von Euler, 20, for discussion). Some of them were probably simple amines, others epinephrinelike. They have been given a variety of names. Because of their non-specific nature and the manner of their extraction it seems unlikely that they are concerned in the development or maintenance of chronic human hypertension. 

Figure 4. Prevention of Pressor Action of Renin and Hypertensin (Angiotonin) by Amine...

Lower curve (rat 183). Effect of a double dose of angiotonin mixed with amine oxidase and shaken for 30 minutes at room temperature. Angiotonin was completely inactivated. After 4 minutes the same dose alone produced a modified pressor response. Rat was hypertensive. 

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