Ring hydroxylation phenylethylamine

On comparing the activities of the five compounds for which numerical estimates are available in all three assays (synephrine, octopamine, phenylethanolamine, norepinephrine and tyramine) the rank orders of potency in the three systems are Crayfish, 1,2,3t4,5 Cockroach, 2,1,3,4,5 Locust 1,2,3t5,4. This indicates a basic similarity in the responses of these preparations. In each case it was found that ring hydroxylation of the phenylethylamine nucleus was not essential for activity, although p-hydroxylation does yield the best activity. This is particularly evident in the crayfish study where a-MAMBA (a-methylaminomethyl benzyl alcohol), the analog of synephrine which lacks ring substitution, was one of the most active compounds tested, and 3-phenylethanolamine, the corresponding analog of OA, is almost as active as OA. The base compound for this series, phenylethylamine, also shows appreciable activity, but only in the crayfish assay. 

In addition to amino acids, a number of phenylethylamine derivatives are taken up by adrenergic nerves and converted by dopamine- -hydroxylase into the corresponding ) -hydroxylated phenylethanolamines. which may then be stored and released (Fig. 12). In addition some phenylethylamines may first be ring hydroxyl-ated by a liver microsomal system, the resulting products taken up into adrenergic nerves and -hydroxylated. This occurs, for example, with amphetamine, which gives rise in certain species to the amines norephedrine and p-hydroxynorq>hedrine which are retained in the tissue stores (Fig. 12). 

Chemical structures of catecholamines produced naturally in humans are shown in Figure 29-1. Epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine are phenylethylamines with hydroxylation on positions three and four of the benzene ring and with an ethylamine moiety on position one. Hydroxyl and methyl substitution on the... 

Other methyl-substituted phenylethylamines (phenylisopropylamines). such as (S)-(+)-amphetamine and (S)-(+)-methamphetamine, which lack both ring substituents I side-chain hydroxyl, are sufficiently lipophilic to cross the blood-brain barrier readily and cause dramatic CNS stimulation, which gives them serious abuse... 

Phenylethylamines (phenethylamines) contain a phenyl ring adjacent to an ethylamine side chain. The phenyl ring is frequently hydroxylated and metho-xylated. The amino group may be methylated. 

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