Purinergic antagonists include clonidine, a potent P 1 antagonist that is also an α 2 and
H 2 agonist (see section 4.3.6), facilitating purine release. Methylxanthines, especially
caffeine (4.241), are potent P 1 antagonists. When one considers the enormous amount
of caffeine consumed in the world, this discovery is significant for understanding the
symptoms of caffeine addiction. Many classes of A 1 receptor antagonists have been
described; the majority of these have traditionally been xanthine analogs. Likewise, a
number of A 2A receptor antagonists based on xanthines and related heterocyclic core
structures have been described. Finally, a structurally diverse set of A 3 receptor antagonists has recently been identified.
At the time of writing, many compounds based on the adenosine receptor are in preclinical or early clinical development.
Selected References
Overview of Relevant Neuroanatomy and Neurophysiology
M. L. Barr, J. A. Kiernan (1988). The Human Nervous System: An Anatomical Viewpoint, 5th ed.
Philadelphia: Lippincott.
M. Göthert (1985). Role of autoreceptors in the function of the peripheral and central nervous
system. Arzneimittelforschung 35: 1909–1916.
T. Hökfelt, B. Evaritt, B. Meister, T. Melander, M. Schalling, O. Johansson, J. M. Lundberg,
A. L. Hulting, S. Werner, C. Cuello, M. Hemming, C. Ouimet, J. Walaas, P. Greengard,
M. Goldstein (1986). Neurons with multiple messengers, with special reference to neuroendocrine systems. Recent Prog. Hormone Res. 42: 1–70.
P. M. Laduron (1985). Postsynaptic heteroreceptors in the regulation of neuronal transmission.
Biochem. Pharmacol. 34: 467–470.
S. Z. Langer (1981). Presynaptic receptors. Pharmacol. Rev. 32: 337–363.
C. J. Pazoles, J. L. Ives (1985). Cotransmitters in the CNS. Annu. Rep. Med. Chem. 20: 51–60.
L. F. Reichardt, R. B. Kelly (1983). A molecular description of nerve terminal function. Annu.
Rev. Biochem. 52: 871–926.
Acetylcholine and Cholinergic Receptors
E. A. Accili, G. Redaelli, D. DiFrancesco (1998). Two distinct pathways of muscarinic current
responses in rabbit sino-atrial node myocytes. Pflugers Arch. 437: 164.
B. C. Bowman (1986). Mechanisms of action of neuromuscular blocking drugs. In: G. N. Woodruff
(Ed.). Mechanisms of Drug Action, vol. 1. London: Macmillan, pp. 65–96.
O. E. Brodde, M. C. Michel (1999). Adrenergic and muscarinic receptors in the human heart.
Pharmacol. Rev. 51: 651.
W. H. Bunnelle, M. J. Dart, M. R. Schrimpf (2004). Design of ligands for the nicotinic acetylcholine receptors: the quest for selectivity. Curr. Top. Med. Chem. 4: 299–334.
M. P. Caulfield, N. J. M. Birdsall (1998). Classification of muscarinic acetylcholine receptors.
Pharmacol. Rev. 50: 279.
B. M. Conti-Tronconi, M. A. Raftery (1982). The nicotinic cholinergic receptor: correlations of
molecular structure with functional properties. Annu. Rev. Biochem. 51: 491–530.
Y. Dunant, M. Israël (1985). The release of acetylcholine. Sci. Am. 252: 58–66.
R. M. Eglen, S. S. Hedge, N. Watson (1996). Muscarinic receptor subtypes and smooth muscle
function. Pharmacol. Rev. 48: 531.
NEUROTRANSMITTERS AND THEIR RECEPTORS
299
H 2 agonist (see section 4.3.6), facilitating purine release. Methylxanthines, especially
caffeine (4.241), are potent P 1 antagonists. When one considers the enormous amount
of caffeine consumed in the world, this discovery is significant for understanding the
symptoms of caffeine addiction. Many classes of A 1 receptor antagonists have been
described; the majority of these have traditionally been xanthine analogs. Likewise, a
number of A 2A receptor antagonists based on xanthines and related heterocyclic core
structures have been described. Finally, a structurally diverse set of A 3 receptor antagonists has recently been identified.
At the time of writing, many compounds based on the adenosine receptor are in preclinical or early clinical development.
Selected References
Overview of Relevant Neuroanatomy and Neurophysiology
M. L. Barr, J. A. Kiernan (1988). The Human Nervous System: An Anatomical Viewpoint, 5th ed.
Philadelphia: Lippincott.
M. Göthert (1985). Role of autoreceptors in the function of the peripheral and central nervous
system. Arzneimittelforschung 35: 1909–1916.
T. Hökfelt, B. Evaritt, B. Meister, T. Melander, M. Schalling, O. Johansson, J. M. Lundberg,
A. L. Hulting, S. Werner, C. Cuello, M. Hemming, C. Ouimet, J. Walaas, P. Greengard,
M. Goldstein (1986). Neurons with multiple messengers, with special reference to neuroendocrine systems. Recent Prog. Hormone Res. 42: 1–70.
P. M. Laduron (1985). Postsynaptic heteroreceptors in the regulation of neuronal transmission.
Biochem. Pharmacol. 34: 467–470.
S. Z. Langer (1981). Presynaptic receptors. Pharmacol. Rev. 32: 337–363.
C. J. Pazoles, J. L. Ives (1985). Cotransmitters in the CNS. Annu. Rep. Med. Chem. 20: 51–60.
L. F. Reichardt, R. B. Kelly (1983). A molecular description of nerve terminal function. Annu.
Rev. Biochem. 52: 871–926.
Acetylcholine and Cholinergic Receptors
E. A. Accili, G. Redaelli, D. DiFrancesco (1998). Two distinct pathways of muscarinic current
responses in rabbit sino-atrial node myocytes. Pflugers Arch. 437: 164.
B. C. Bowman (1986). Mechanisms of action of neuromuscular blocking drugs. In: G. N. Woodruff
(Ed.). Mechanisms of Drug Action, vol. 1. London: Macmillan, pp. 65–96.
O. E. Brodde, M. C. Michel (1999). Adrenergic and muscarinic receptors in the human heart.
Pharmacol. Rev. 51: 651.
W. H. Bunnelle, M. J. Dart, M. R. Schrimpf (2004). Design of ligands for the nicotinic acetylcholine receptors: the quest for selectivity. Curr. Top. Med. Chem. 4: 299–334.
M. P. Caulfield, N. J. M. Birdsall (1998). Classification of muscarinic acetylcholine receptors.
Pharmacol. Rev. 50: 279.
B. M. Conti-Tronconi, M. A. Raftery (1982). The nicotinic cholinergic receptor: correlations of
molecular structure with functional properties. Annu. Rev. Biochem. 51: 491–530.
Y. Dunant, M. Israël (1985). The release of acetylcholine. Sci. Am. 252: 58–66.
R. M. Eglen, S. S. Hedge, N. Watson (1996). Muscarinic receptor subtypes and smooth muscle
function. Pharmacol. Rev. 48: 531.
NEUROTRANSMITTERS AND THEIR RECEPTORS
299