title: Local anesthetic properties of opioids and phencyclidines: interaction with the voltage-dependent, batrachotoxin binding site in sodium channels.
abstract: [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.
authors.forename: C R
authors.initials: CR
authors.lastname: Creveling
authors.forename: E T
authors.initials: ET
authors.lastname: McNeal
authors.forename: G A
authors.initials: GA
authors.lastname: Lewandowski
authors.forename: M
authors.initials: M
authors.lastname: Rafferty
authors.forename: E H
authors.initials: EH
authors.lastname: Harrison
authors.forename: A E
authors.initials: AE
authors.lastname: Jacobson
authors.forename: K C
authors.initials: KC
authors.lastname: Rice
authors.forename: J W
authors.initials: JW
authors.lastname: Daly
mesh_terms: D000779:Anesthetics, Local / Q000378:metabolism; D000818:Animals; D001496:Batrachotoxins / Q000378:metabolism*; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism*; D009294:Narcotics / Q000378:metabolism*; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects; D017450:Receptors, Opioid, mu; D017480:Receptors, sigma
chemical_list: D000779:Anesthetics, Local; D001496:Batrachotoxins; D007473:Ion Channels; D009294:Narcotics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D017480:Receptors, sigma; D010622:Phencyclidine