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N‐ARALKYL SUBSTITUTION INCREASES THE AFFINITY OF ADRENERGIC DRUGS FOR THE α‐ADRENOCEPTOR IN RAT LIVER
Author(s) -
AGGERBECK MARTINE,
GUELLAEN GEORGES,
HANOUNE JACQUES
Publication year - 1979
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1979.tb17344.x
Subject(s) - chemistry , isoprenaline , stereochemistry , agonist , pindolol , antagonist , orciprenaline , partial agonist , alpha (finance) , receptor , adrenergic antagonist , adrenergic receptor , biochemistry , endocrinology , biology , medicine , construct validity , nursing , stimulation , patient satisfaction
1 The α‐adrenoceptor of rat liver plasma membranes was studied by use of the specificα‐antagonist [ 3 H]‐dihydroergocryptine ([ 3 H]‐DHEC). Catecholamines and adrenergic compounds displayed an order of affinity that is typical of anα‐receptor. Nevertheless, protokylol, a potent β‐adrenoceptor agonist, exhibited a higher affinity than that of adrenaline forα‐sites. This result might be due to its bulky substituent on the amino group. 2 Further displacement experiments between [ 3 H]‐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 forα‐sites (20 μ m < K D < 500 μ m ), whereas an N‐aralkyl one increased the affinity (0.17 μ m < K D < 4.6 μ m ). 3 It is concluded that a substitution on the amino group by a bulky, hydrophobic moiety enhances the affinity of drugs for the α‐adrenoceptors.