By Dr. Rae R. Matsumoto (auth.), Tsung-Ping Su, Rae R. Matsumoto, Wayne D. Bowen (eds.)
Sigma receptors are promising drug improvement objectives for a number of neurological, psychiatric, oncological, immunological, cardiovascular, ophthalmological, and gastrointestinal issues. they're structurally precise proteins which are specific from classical G protein-coupled receptors, ionotropic receptors, or receptor tyrosine kinases. With subtypes at the moment recognized, they modulate telephone survival and excitability, and subserve many severe services within the physique. Endogenous ligands for those receptors are unknown, even though present clues element to neurosteroids.
This booklet presents a well timed replace at the medicinal chemistry, telephone biology, and scientific implications of sigma receptors. It places the data in a ancient viewpoint to aid new comers to the sector effectively navigate the complicated early historical past surrounding those proteins, and gives a launching aspect for the advance of fascinating, new research.
Sigma Receptors: Chemistry, mobilephone Biology and medical Implications should be a invaluable device for pharmacologists, medicinal chemists, mobilephone biologists, molecular biologists, clinicians, and others attracted to a concise, state of the art evaluate of the sigma receptor box with a selected view in the direction of novel healing advances.
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Sigma receptors are promising drug improvement pursuits for a number of neurological, psychiatric, oncological, immunological, cardiovascular, ophthalmological, and gastrointestinal issues. they're structurally specified proteins which are specific from classical G protein-coupled receptors, ionotropic receptors, or receptor tyrosine kinases.
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Additional info for Sigma Receptors: Chemistry, Cell Biology and Clinical Implications
Haloperidol (13) has been shown to possess high affinity for a-receptors, with a slight preference for CTI over QI (30). When the ketone was reduced to give reduced haloperidol (14), the dopamine D2 affinity of haloperidol was greatly decreased, to give a compound relatively selective for a receptors over other systems. These studies led to the development of the related E-5842 (15) as a <3\ agent, with excellent selectivity over a range of other biological systems. E-5842 has been shown to possess promise as an antipsychotic agent (31).
Eur J Pharmacol 1993, 243:249-254. 100. Monnet FP, Debonnel G, de Montigny C. The cytochromes P-450 are not involved in the modulation of the N-methyl-D-aspartate response by sigma Iigands in the rat CA3 dorsal hippocampus. Synapse 1993, 13:30-38. 101. Kennedy C, Henderson G. An examination of the putative sigma-receptor in the mouse isolated vas deferens. Br J Pharmacol 1989, 98:429-436. 102. SuT-P, Wu XZ. Guinea pig vas deferens contains sigma but not phencyclidine receptors. Neurosci Lett 1990, 108:341-345.
The merits of this hypothesis are discussed elsewhere in this volume. 2,3 Figure 2-2. Phenylethylene diamine-based a ligands 3. a SELECTIVE AGENTS Initial studies with early a ligands were limited due to the effects on other systems influencing the pharmacology of the ligand. Obviously, what was needed were compounds that did not interact with other biological systems. One of the most widely studied class of compounds are the phenylethylene diamines: the protypical member of this class is BD1008 (4) (Figure 2-2) (24).