Molecular aspects of the receptor activation by imidazolines: an overview

  • P. N. Patil
  • D. R. Feller
  • D. D. Miller
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 34)


Based on the pharmacological activity of chiral imidazolines the steric requirements for the activation of the α-adrenoceptor are provided. Importantly, the sequence of interaction of the critical groups of the asymmetric carbon of imidazolines and catecholamines with the α-adrenoceptor is postulated. Thus, initial determinants of molecular efficacy are hypothesized. The effect of aromatic fluoro-substitution and introduction of a double bond in the imidazoline moiety on the pharmacologic activity is discussed. The unique mechanism of non-adrenergic vascular activity of isothiocyanato-tolazoline is presented.


Human Platelet Rostral Ventrolateral Medulla Catechol Moiety Steric Requirement Adrenergic Drug 
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  1. Ahn CH, Hamada A, Miller DD, Feller DR (1986) Alpha-adrenoceptor-mediated actions of optical isomers and desoxy analogs of cateeholimidazoline and norepinephrine in human platelets: in vitro. Biochem Pharmacol 35: 4095–4102PubMedCrossRefGoogle Scholar
  2. Banning JW, Rice PJ, Miller DD, Ruffolo RR, Hamada A, Patil PN (1984) Differences in the adrenoceptor activation of stereoisomeric catecholimidazolines and catecholamines In: Fleming WW, et al (eds) Neuronal and extraneuronal events in autonomic pharmacology. Raven Press, New York, pp 167–180Google Scholar
  3. Bousquet P, Feldman J, Schwartz J (1984) Central cardiovascular effects of alpha adrenergic drugs: differences between catecholamines and imidazolines. J Pharmacol Exp Ther 230: 232–236PubMedGoogle Scholar
  4. Brown CM, Mackinnon AC, McGrath JC, Spedding M, Kilpatrick AT (1990) α2-Adrenoceptor subtypes and imidazoline-like binding sites in the rat brain. Br J Pharmacol 99: 803–809Google Scholar
  5. Clark RD, Michel AD, Whiting R (1986) Pharmacology and structure-activity relationships of α2-adrenoceptor antagonists. In: Ellis G-P, West GB (eds) Progress in medicinal chemistry, vol 23. Elsevier, New York, pp 1–39Google Scholar
  6. Ernsberger P, Giuliano R, Willette RN, Reis DJ (1990) Role of imidazole receptors in the vasodepressor response to clonidine analogs in the rostral ventrolateral medulla. J Pharmacol Exp Ther 253: 408–418PubMedGoogle Scholar
  7. Fuder H, Nelson WL, Miller DD, Patil PN (1981) Alpha adrenoceptors of rabbit aorta and stomach fundus. J Pharmacol Exp Ther 217: 1–9PubMedGoogle Scholar
  8. Han C, Abel PW, Minneman KP (1987) Heterogeneity of aradrenergic receptors revealed by chlorethylclonidine. Mol Pharmacol 32: 505–510PubMedGoogle Scholar
  9. Kirk KL, Creveling CR (1984) The chemistry and biology of ring-fluorinated biogenic amines. Med Res Rev 4: 189–220PubMedCrossRefGoogle Scholar
  10. Lamba-Kanwal VK, Hamada A, Adejare A, Clark MT, Miller DD, Patil PN (1988) Activation of alpha-1 adrenoreceptors of rat aorta by analogs of imidazoline. J Pharmacol Exp Ther 245: 793–797PubMedGoogle Scholar
  11. Michel MC, Regan JW, Gerhardt MA, Neubig RR, Insel PA, Motulsky HJ (1990) Noradrenergic [3H] idazoxan binding sites are physically distinct from α2-adrenergic receptors. Mol Pharmacol 37: 65–68PubMedGoogle Scholar
  12. Miller DD, Hsu FL, Ruffolo Jr RR, Patil PN (1976) Stereochemical studies of adrenergic drugs. Optically active derivatives of imidazolines. J Med Chem 19: 1382–1384Google Scholar
  13. Miller DD, Hamada A, Clark MT, Adejare A, Patil PN, Shams G, Romstedt KJ, Kim SU, Instrasuksri U, Mckenzie JL, Feller DR (1990) Synthesis and a2-adrenoceptor effects of substituted catecholimidazoline and catecholimidazole analogues in human platelets. J Med Chem 33: 1138–1144PubMedCrossRefGoogle Scholar
  14. Oriowo MA, Bevan J A (1990) Chlorethylclonidine unmasks a non-α-adrenoceptor noradrenaline binding site in the rat aorta. Eur J Pharmacol 178: 243–246PubMedCrossRefGoogle Scholar
  15. Parini A, Coupry I, Graham RM, Uzielli I, Atlas D, Lanier, SM (1989) Characterization of an imidazoline/guanidium receptive site distinct from the α2- adrenergic receptor. J Biol Chem 264: 11874–11878PubMedGoogle Scholar
  16. Patil PN, Miller DD, Trendelenburg U (1974) Molecular geometry and adrenergic drug activity. Pharmacol Rev 26: 323–392PubMedGoogle Scholar
  17. Pullman B, Coubeils JL, Courriere PH, Gervois JP (1972) Quantum mechanical study of the conformational properties of phenethylamines of biochemical and medicinal interest. J Med Chem 15: 17–21PubMedCrossRefGoogle Scholar
  18. Rice P. J. (1985) Molecular aspects of the activation of alpha-adrenergic receptors. Dissertation, The Ohio State University, Columbus, OH, U.S.A.Google Scholar
  19. Rice PJ, Hamada A, Miller DD, Patil PN (1987) Asymmetric catecholimidazolines and catecholamidines: affinity and efficacy relations at the alpha adrenoreceptor in rat aorta. J Pharmacol Exp Ther 242: 121–130PubMedGoogle Scholar
  20. Rice PJ, Miller DD, Sokoloski TD, Patil PN (1989) Pharmacologic implications of α-adrenoreceptor interactive parameters for epinephrine enantiomers in the rat vas deferens. Chirality 1: 14–19PubMedCrossRefGoogle Scholar
  21. Ruffolo RR (1983) Structure-activity relationship of alpha-adrenoceptor agonists In: Kunos G (ed) Adrenoceptors and catecholamines action. Wiley, New York, pp 1–50Google Scholar
  22. Ruffolo RR, Turowski B, Patil PN (1977) Lack of cross desensitization between two structurally dissimilar α-adrenoceptor agonists. J Pharm Pharmacol 29: 378–380PubMedCrossRefGoogle Scholar
  23. Sanders J, Miller DD, Patil PN (1975) Alpha adrenergic and histaminergic effects of tolazoline-like imidazolines. J Pharmacol Exp Ther 195: 362–371PubMedGoogle Scholar
  24. Sengupta JN, Hamada A, Miller DD, Patil PN (1987) Interaction of enantiomers of hydroxy tolazoline with adrenoceptors. Naunyn-Schmiedebergs Arch Pharmacol 335: 391–396PubMedCrossRefGoogle Scholar
  25. Sneader W (1985) Drug discovery: the evolution of modern medicines. Wiley, New York, p 105Google Scholar
  26. Strader CD, Sigal IS, Dixon RAF (1989) Genetic approaches to the determination of structure function relationships of G protein-coupled receptors. TIPS [Suppl 26–30]Google Scholar
  27. Starke K (1981) Presynaptic receptors. Ann Rev Pharmacol Toxicol 21: 7–30CrossRefGoogle Scholar
  28. Venkataraman BV, Hamada A, Shams G, Miller DD, Feller DR, Patil PN (1989) Paradoxical effects of isothiocyanate analog of tolazoline on rat aorta and human platelets. Blood Vessels 26: 335–346PubMedGoogle Scholar
  29. Venkataraman BV, Sham G, Hamada A, Amemiya Y, Tantishaiyakul V, Hsu F, Fashempour J, Romstedt KJ, Miller DD, Feller DR, Patil PN (1991) Structure- activity studies of new imidazolines on adrenoceptors of rat aorta and human platelets. Naunyn-Schmiedebergs Arch Pharmacol 344: 454–463PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • P. N. Patil
    • 1
  • D. R. Feller
    • 1
  • D. D. Miller
    • 1
  1. 1.College of Pharmacy, Divisions of Pharmacology and Medicinal ChemistryOhio State UniversityColumbusUSA

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