The potential of subtype-selective neuronal nicotinic acetylcholine receptor agonists as therapeutic agents
| Autor: | Nicholas D. P. Cosford, Jean-Michel Vernier, Tadimeti S. Rao, Gonul Velicelebi, Aida I. Sacaan, M.M. Harpold, Robert Siegel, Frederique Menzaghi, K. A. Stauderman, Laura E. Chavez-Noriega, L.A. McDonald, Bruno Bontempi, Edwin C. Johnson, Carla Suto, M. Akong, Mark S. Washburn, G. K. Lloyd |
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| Rok vydání: | 1998 |
| Předmět: |
Neurons
Biological activity General Medicine Pharmacology Receptors Nicotinic General Biochemistry Genetics and Molecular Biology Substrate Specificity Nicotine chemistry.chemical_compound Nicotinic acetylcholine receptor Nicotinic agonist chemistry Epibatidine medicine Animals Humans Nicotinic Agonists General Pharmacology Toxicology and Pharmaceutics Neurotransmitter Neuroscience Ion channel linked receptors medicine.drug Acetylcholine receptor |
| Zdroj: | Life sciences. 62(17-18) |
| ISSN: | 0024-3205 |
| Popis: | Neuronal nicotinic acetylcholine receptors (NAChRs) are pentameric ligand-gated ion channel receptors which exist as different functional subunit combinations which apparently subserve different physiological functions as indicated by molecular biological and pharmacological techniques. It is possible to design and synthesize novel compounds that have greater selective affinities and efficacies than nicotine for different NAChRs, which should translate into different behavioral profiles and therapeutic potentials. Examples of NAChR agonists studied are nicotine, SIB-1508Y, SIB-1553A and epibatidine. These compounds have different degrees of selectivity for human recombinant NAChRs, different neurotransmitter release profiles in vitro and in vivo and differential behavioral profiles. Preclinical studies suggest that SIB-1508Y is a candidate for the treatment of the motor and cognitive deficits of Parkinson's disease, whereas SIB-1553A appears to have potential as a candidate for the treatment of Alzheimer's disease. Epibatidine has a strong analgesic profile, however the ratio between pharmacological activity and undesirable effects is so low that it is difficult to envisage the use of this compound therapeutically. Nicotine has a broad profile of pharmacological activity, for instance demonstrating activity in models for cognition and analgesia. As for epibatidine, the adverse effects of nicotine severely limits its therapeutic use in humans. The discovery of subtype-selective NAChR agonists such as SIB-1508Y and SIB-1553A provides a new class of neuropsychopharmacological agents with better therapeutic ratios than non-specific agents such as nicotine. |
| Databáze: | OpenAIRE |
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