Conformational effects on the activity of drugs. 5. Pharmacological properties of 2-(p-nitrophenyl)-4-isopropylmorpholine, a cyclic analog of INPEA.
2-(p-Nitrophenyl)-4-isopropylmorphine (V), an analog of 1-(p-nitrophenyl)-2-isopropylaminoethanol (INPEA, I) in which the OCHCHN chain of I is locked in a morpholine ring, loses the beta-receptor blocking activity of I on various isolated preparations. The same ineffectiveness is observed in the O-methyl (II), N-methyl (III), and N,O-dimethyl analog (IV) of I. However, some other properties which are present in I, such as inhibitory effect on acetylcholine or on 5-HT, intrinsic alpha-sympathomimetic activity, and potentiation of catecholamines, are maintained; this demonstrates a complete dissociation of these effects from beta-receptor blockade. The interactions with the alpha-adrenoceptors and with the uptake mechanism are discussed on the basis of the structure-activity relationship between I and its analogs II-V.
D000818:Animals; D003106:Colon / Q000187:drug effects; D003500:Cyclization; D004558:Electric Stimulation; D004983:Ethanolamines / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
D004983:Ethanolamines; D009025:Morpholines; D011941:Receptors, Adrenergic