Local anesthetic properties of opioids and phencyclidines: Interaction with the voltage-dependent, batrachotoxin binding site in sodium channels
| Autor: | E.H. Harrison, John W. Daly, G. A. Lewandowski, Cyrus R. Creveling, Kenner C. Rice, and Arthur E. Jacobson, Michael F. Rafferty, E. T. McNeal |
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| Rok vydání: | 1985 |
| Předmět: |
Narcotics
Stereochemistry Guinea Pigs Allosteric regulation Receptors Opioid mu Phencyclidine In Vitro Techniques complex mixtures Ion Channels Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology medicine Animals Receptors sigma Potency Anesthetics Local Batrachotoxins Binding site Ion channel Cerebral Cortex Binding Sites Endocrine and Autonomic Systems Chemistry Sodium channel General Medicine Rats A-site Neurology Receptors Opioid Batrachotoxin medicine.drug |
| Zdroj: | Neuropeptides. 5:353-356 |
| ISSN: | 0143-4179 |
| DOI: | 10.1016/0143-4179(85)90026-5 |
| Popis: | [3H]Batrachotoxinin-A 20-alpha-benzoate ([3H]BTX-B) binds specifically and with high affinity (Kd = 30 nM) to a site on voltage-dependent Na+ channels. Compounds with local anesthetic activity inhibit the binding of [3H]BTX-B by a mutually exclusive, allosteric mechanism. The potential local anesthetic potency of a series of 23 opioids and phencyclidine-like compounds has been estimated by their inhibition of [3H]BTX-B binding to Na+ channels in a preparation of synaptoneurosomes from guinea pig cerebral cortex. The potency of these compounds were also tested as inhibitors of the specific binding of [3H]phencyclidine ([3H]PCP) to a high affinity site on rat brain membranes. Opioids such as morphine and codeine show little affinity for the [3H]BTX-B binding site or for the [3H]PCP binding site. Other analgesics, many of the PCP-like compounds and dioxadrol derivatives are potent versus [3H]BTX-B binding and display both stereospecificity and high affinity towards the PCP-binding site. However, there was no correlation between local anesthetic potency assessed as antagonism of [3H]BTX-B binding and affinity towards the PCP site. Five classical local anesthetics had no affinity for the PCP-site, but did displace [3H]BTX-B from its binding site. |
| Databáze: | OpenAIRE |
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