N-Aralkyl substitution increases the affinity of adrenergic drugs for the alpha-adrenoceptor in rat liver.

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Aggerbeck M, Guellaen G, Hanoune J

N-Aralkyl substitution increases the affinity of adrenergic drugs for the alpha-adrenoceptor in rat liver.

Br J Pharmacol. 1979 Jan;65(1):155-9.

PubMed ID

216448 [ View in PubMed

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Abstract

1 The alpha-adrenoceptor of rat liver plasma membranes was studied by use of the specific alpha-antagonist [3H]-dihydroergocryptine ([3H]-DHEC). Catecholamines and adrenergic compounds displayed an order of affinity that is typical of an alpha-receptor. Nevertheless, protokylol, a potent beta-adrenoceptor agonist, exhibited a higher affinity than that of adrenaline for alpha-sites. This result might be due to its bulky substituent on the amino group. 2 Further displacement experiments between [3H]-DHEC and four pairs of drugs differently substituted on the amino group (isoprenaline vs Cc-25, orciprenaline vs fenoterol, AH 3474 vs labetalol, pindolol vs hydroxybenzylpindolol) provided evidence that N-alkyl substitution decreased the affinity for alpha-sites (20 micromolar less than KD less than 200 micromolar), whereas an N-aralkyl one increased the affinity (0.17 micromloar less than KD less than 4.6 micromolar). 3 It is concluded that a substitution on the amino group by a bulky, hydrophobic moiety enhances the affinity of drugs for the alpha-adrenoceptors.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Protokylol	Beta-2 adrenergic receptor	Protein	Humans	Yes	Agonist	Details