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Adrenergic Pharmacology: Focus on the Central Nervous System

Published online by Cambridge University Press:  07 November 2014

Andre S. Pupo  and
Kenneth P. Minneman
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Abstract

Norepinephrine and epinephrine are involved in the control of several important functions of the central nervous system (CNS), including sleep, arousal, mood, appetite, and autonomic outflow. Catecholamines control these functions through activation of a family of adrenergic receptors (ARs). The ARs are divided into three subfamilies (α1, α2, and β) based on their pharmacologic properties, signaling mechanisms, and structure. ARs in the CNS are targets for several therapeutic agents used in the treatment of depression, obesity, hypertension, and other diseases. Not much is known, however, about the role of specific AR sub-types in the actions of these drugs. In this paper, we provide an overview of adrenergic pharmacology in the CNS, focusing on the pharmacologic properties of subtype-selective AR agonists and antagonists, the accessibility of these drugs to the CNS, and the distribution of ARs in different areas of the brain.

Type
Feature Articles
Information
CNS Spectrums , Volume 6 , Issue 8: Advances in the Neurobiology of Norepinephrine and its Relevance to Psychiatric Disorders , August 2001 , pp. 656 - 662
Copyright
Copyright © Cambridge University Press 2001

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References

REFERENCES

1. Foote, SL, Bloom, FE, Aston-Jones, G. Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev. 1983;63:844–914.CrossRefGoogle ScholarPubMed
2. Hökfelt, T, Johansson, O, Goldstein, M. Central catecholamine neurons as revealed by immunohistochemistry with special reference to adrenaline neurons. In: Björklund, A, Hökfelt, T, ed. Handbook of chemical neuroanatomy. Classical Transmitters in the CNS, Part I. Amsterdam, the Netherlands: Elsevier; 1984:157–276.Google Scholar
3. Bylund, DB, Eikenberg, DC, Hieble, JP et al. , International Union of Pharmacology nomenclature of adrenoceptors. Pharmacol Rev. 1994;46:121–136.Google ScholarPubMed
4. Hieble, JP, Bylund, DB, Clarke, DE et al. , International Union of Pharmacology. X. Recommendation for nomenclature of alpha 1-adrenoceptors: consensus update. Pharmacol Rev. 1995;47:267–270.Google ScholarPubMed
5. Hall, RA, Premont, RT, Chow, CW et al. , The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. Nature. 1998;392:626–630.CrossRefGoogle ScholarPubMed
6. Hu, LA, Tang, Y, Miller, WE et al. , Beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors. J Biol Chem. 2000;275:38659–38666.CrossRefGoogle ScholarPubMed
7. Ahlquist, RP. A study of adrenotropic receptors. Am J Physiol. 1948;153:586–600.CrossRefGoogle ScholarPubMed
8. Lands, AM, Arnold, A, MeAuliff, JP, Luduena, FP, Brown, TG. Differentiation of receptor systems activated by sympathomimetic amines. Nature. 1967;214:597–598.CrossRefGoogle ScholarPubMed
9. Emorine, LJ, Marullo, S, MM, Briend-Sutren et al. , Molecular characterization of the human beta 3-adrenergie receptor. Science. 1989;245:1118–1121.CrossRefGoogle ScholarPubMed
10. Sennitt, MV, Kaumann, AJ, Molenaar, P et al. , The contribution of classical (beta1/2-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta3-adrenoceptor agonists of differing selectivities. J Pharmacol Exp Ther. 1998;285:1084–1095.Google Scholar
11. Minneman, KP, Theroux, TL, Hollinger, S, Han, C, Esbenshade, TA. Selectivity of agonists for cloned alpha 1-adrenergic receptor subtypes. Mol Pharmacol. 1994;46:929–936.Google ScholarPubMed
12. Nagarathnam, D, Wetzel, JM, Miao, SW et al. , Design and synthesis of novel alphala adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia. J Med Chem. 1998;41:5320–5333.CrossRefGoogle Scholar
13. Foglar, R, Shibata, K, Horie, K, Hirasawa, A, Tsujimoto, G. Use of recombinant alpha 1-adrenoceptors to characterize subtype selectivity of drugs for the treatment of prostatic hypertrophy. Eur J Pharmacol. 1995;288:201–207.CrossRefGoogle ScholarPubMed
14. Boer, R, Grassegger, A, Schudt, C, Glossmann, H. (+)-Niguldipine binds with very high affinity to Ca2+ channels and to a subtype of alpha I adrenoceptors. Eur J Pharmacol. 1989;172:131–145.CrossRefGoogle ScholarPubMed
15. Wetzel, JM, Miao, SW, Forray, C et al. , Discovery of alpha la-adrenergie receptor antagonists based on the L-type Ca2+ channel antagonist niguldipine. J Med Chem. 1995;38:1579–1581.CrossRefGoogle ScholarPubMed
16. Gross, G, Hanft, G, Rugevics, C. 5-methyl-urapidil discriminates between subtypes of the alpha 1-adrenoceptor. Eur J Pharmacol. 1988;151:333–335.CrossRefGoogle ScholarPubMed
17. Morrow, AL, Creese, I. Characterization of alpha 1-adrenergic receptor sub-types in rat brain: a reevaluation of [3H]WB4104 and [3H]prazosin binding. Mol Pharmacol. 1986;29:321–330.Google Scholar
18. Goetz, AS, King, HK, Ward, SD et al. , BMY 7378 is a selective antagonist of the D subtype of alpha 1-adrenoceptors. Eur J Pharmacol. 1995;272:R5–R6.CrossRefGoogle Scholar
19. MacMillan, LB, Hein, L, Smith, MS, Piascik, MT, Limbird, LE. Central hypotensive effects of the alpha2a-adrenergic receptor subtype. Science. 1996;273:801–803.CrossRefGoogle ScholarPubMed
20. Rohrer, DK, Kobilka, BK. Insights from in vivo modification of adrenergic receptor gene expression. Annu Rev Pharmacol Toxicol. 1998;38:351–373.CrossRefGoogle ScholarPubMed
21. Mizobe, T, Maghsoudi, K, Sitwala, K et al. , Antisense technology reveals the alpha2A adrenoceptor to be the subtype mediating the hypnotic response to the highly selective agonist, dexmedetomidine, in the locus coeruleus of the rat. J Clin Invest. 1996;98:1076–1080.CrossRefGoogle Scholar
22. Pratt, WB, Taylor, P. Principles of Drug Action: The Basis of Pharmacology. New York, NY: Churchill Livingstone; 1990.Google Scholar
23. Hardebo, JE, Owman, C. Barrier mechanisms for neurotransmitter monoamines and their precursors at the blood-brain interface. Ann Neurol. 1980;8:1–31.CrossRefGoogle ScholarPubMed
24. Heal, DJ. Phenylephrine-induced activity in mice as a model of central alpha 1-adrenoceptor function. Effects of acute and repeated administration of antidepressant drugs and electroconvulsive shock. Neumpharmacology. 1984;23:1241–1251.CrossRefGoogle Scholar
25. Mignot, E, Guilleminault, C, Bowersox, S, Rappaport, A, Dement, WC. Role of central alpha-1 adrenoceptors in canine narcolepsy. J Clin Invest. 1988;82:885–894.CrossRefGoogle ScholarPubMed
26. Jonge, AD, van Meel, JC, Timmermans, PB, van Zwieten, PA. A lipophilic, selective alphal-adrenoceptor agonist: 2-(2-chloro-5-trifluoromethylphenylimino)imida-zolidine (St587). Life Sci. 1981:28:2009–2016.CrossRefGoogle Scholar
27. Pichler, L, Kobinger, W. Possible function of alpha 1-adrenoceptors in the CNS in anaesthetized and conscious animals. Eur J Pharmacol. 1985;107:305–311.CrossRefGoogle ScholarPubMed
28. Hoefke, W, Kobinger, W, Walland, A. Relationship between activity and structure in derivatives of clonidine. Arzneimittelforschung. 1975;25:786–793.Google ScholarPubMed
29. Paalzow, LK, Edlund, PO. Pharmacokinetics of clonidine in the rat and cat. J Pharmacokinet Biopharm. 1979;7:481–494.CrossRefGoogle ScholarPubMed
30. Isaac, L. Brain sites for the antihypertensive action of clonidine. Prog Clin BiolRes. 1981;71:29–39.Google ScholarPubMed
31. van Zwieten, PA. Centrally acting antihypertensives: a renaissance of interest. Mechanisms and haemodynamics. J Hypertens Suppl. 1997;15:S3–S8.CrossRefGoogle ScholarPubMed
32. Bylund, DB. Pharmacological characteristics of alpha-2 adrenergic receptor subtypes. Ann N YAcad Sci. 1995;763:1–7.CrossRefGoogle ScholarPubMed
33. Khan, ZP, Ferguson, CN, Jones, RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia. 1999;54:146–165.CrossRefGoogle ScholarPubMed
34. Oldendorf, WH. Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. Am J Physiol. 1971;221:1629–1639.CrossRefGoogle ScholarPubMed
35. Conway, PG, Tejani-Butt, S, Brunswick, DJ. Interaction of beta adrenergic agonists and antagonists with brain beta adrenergic receptors in vivo. J Pharmacol Exp Ther. 1987;241:755–762.Google ScholarPubMed
36. O'Donnell, JM, Frazer, A. Effects of clenbuterol and antidepressant drugs on beta adrenergic receptor/N-protein coupling in the cerebral cortex of the rat. J Pharmacol Exp Ther. 1985;234:30–36.Google ScholarPubMed
37. Crissman, AM, Makhay, MM, JM, O'Donnell. Discriminative stimulus effects of centrally administered isoproterenol in rats: mediation by beta-1 adrenergic receptors. Psychopharmacology (Bed). 2001;154:70–75.CrossRefGoogle ScholarPubMed
38. Nisoli, E, Carruba, MO. Pharmacological properties of beta 3-adrenoceptors. Trends Pharmacol Sci. 1997;18:257–258.CrossRefGoogle ScholarPubMed
39. Taylor, JA, Twomey, TM, von Wittenau, MS. The metabolic fate of prazosin. Xenobiotica. 1977;7:357–364.CrossRefGoogle ScholarPubMed
40. Jaillon, P. Clinical pharmacokinetics of prazosin. Clin Pharmacokinet. 1980;5:365–376.CrossRefGoogle ScholarPubMed
41. Menkes, DB, Baraban, JM, Aghajanian, GK. Prazosin selectively antagonizes neuronal responses mediated by alphal-adrenoceptors in brain. Naunyn Schmiedebergs Arch Pharmacol. 1981;317:273–275.CrossRefGoogle Scholar
42. Stone, EA, Lin, Y, Itteera, A, Quartermain, D. Pharmacological evidence for the role of central alpha 1B-adrenoceptors in the motor activity and spontaneous movement of mice. Neuropharmacology. 2001;40:254–261.CrossRefGoogle ScholarPubMed
43. Ho, AK, Hoffman, DB, Gershon, S, Loh, HH. Distribution and metabolism of tritiated yohimbine in mice. Arch Int Pharmacodyn Ther. 1971:194:304–315.Google ScholarPubMed
44. Millan, MJ, Colpaert, FC. Alpha 2 receptors mediate the antinociceptive action of 8-OH-DPAT in the hot-plate test in mice. Brain Res. 1991;539:342–346.CrossRefGoogle ScholarPubMed
45. Hayes, A, Cooper, RG. Studies on the absorption, distribution and excretion of propranolol in rat, dog and monkey. J Pharmacol Exp Ther. 1971;176:302–311.Google Scholar
46. Street, JA, Hemsworth, BA, Roach, AG, Day, MD. Tissue levels of several radiolabeled beta-adrenoceptor antagonists after intravenous administration in rats. Arch Int Pharmacodyn Ther. 1979;237:180–190.Google ScholarPubMed
47. Price, DT, Lefkowitz, RJ, Caron, MG, Berkowitz, D, Schwinn, DA. Localization of mRNA for three distinct alpha 1-adrenergic receptor sub-types in human tissues: implications for human alpha-adrenergic physiology. Mol Pharmacol. 1994;45:171–175.Google Scholar
48. Price, DT, Chari, RS, Berkowitz, DE, Meyers, WC, Schwinn, DA. Expression of alpha 1-adrenergic receptor subtype mRNA in rat tissues and human SK-N-MC neuronal cells: implications for alpha 1-adrenergic receptor subtype classification. Mol Pharmacol. 1994;46:221–226.Google ScholarPubMed
49. Pieribone, VA, Nicholas, AP, Dagerlind, A, Hokfelt, T. Distribution of alpha 1 adrenoceptors in rat brain revealed by in situ hybridization experiments utilizing subtype-specific probes. J Neurosci. 1994;14:4252–4268.CrossRefGoogle ScholarPubMed
50. McCune, SK, Voigt, MM, Hill, JM. Expression of multiple alpha adrenergic receptor subtype messenger RNAs in the adult rat brain. Neuroscience. 1993;57:143–151.CrossRefGoogle ScholarPubMed
51. Day, HE, Campeau, S, Watson, SJ, Akil, H. Distribution of alpha la-, alpha lb- and alpha ld-adrenergic receptor mRNA in the rat brain and spinal cord. J Chem Neumanat. 1997;13:115–139.Google Scholar
52. Nicholas, AP, Pieribone, V, Hokfelt, T. Distributions of mRNAs for alpha-2 adrenergic receptor subtypes in rat brain: an in situ hybridization study. J Comp Neurol. 1993;328:575–594.CrossRefGoogle Scholar
53. Scheinin, M, Lomasney, JW, DM, Hayden-Hixson et al. , Distribution of alpha 2-adrenergic receptor subtype gene expression in rat brain. Brain Res Mol Brain Res. 1994;21:133–149.CrossRefGoogle ScholarPubMed
54. Rosin, DL, Talley, EM, Lee, A et al. , Distribution of alpha 2C-adrenergic receptor-like immunoreactivity in the rat central nervous system. J Comp Neurol. 1996;372:135–165.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
55. Talley, EM, Rosin, DL, Lee, A, Guyenet, PG, Lynch, KR. Distribution of alpha 2A-adrenergic receptor-like immunoreactivity in the rat central nervous system. J Comp Neurol. 1996;372:111–134.3.0.CO;2-6>CrossRefGoogle ScholarPubMed
56. Lee, A, Wissekerke, AE, Rosin, DL, Lynch, KR. Localization of alpha2Cadrenergic receptor immunoreactivity in catecholaminergic neurons in the rat central nervous system. Neuroscience. 1998;84:1085–1096.CrossRefGoogle ScholarPubMed
57. Nicholas, AP, Pieribone, VA, Hokfelt, T. Cellular localization of messenger RNA for beta-1 and beta-2 adrenergic receptors in rat brain: an in situ hybridization study. Neuroscience. 1993;56:1023–1039.CrossRefGoogle Scholar
58. Summers, RJ, Papaioannou, M, Harris, S, Evans, BA. Expression of beta 3-adrenoceptor mRNA in rat brain. Br J Pharmacol. 1995;116:2547–2548.CrossRefGoogle ScholarPubMed
59. Nicholas, AP, Hokfelt, T, Pieribone, VA. The distribution and significance of CNS adrenoceptors examined with in situ hybridization. Trends Pharmacol Sci. 1996;17:245–255.CrossRefGoogle ScholarPubMed
60. Tsujii, S, Bray, GA. Food intake of lean and obese Zucker rats following ventricular infusions of adrenergic agonists. Brain Res. 1992;587:226–232.CrossRefGoogle ScholarPubMed