title: 4-Bromoacetamidoprocaine: an affinity ligand for brain muscarinic and nicotinic cholinergic receptors.
abstract: This study describes the synthesis, receptor binding characteristics, and some behavioral effects of p-bromoacetamidoprocaine (BAP), a new affinity ligand for brain muscarinic and nicotinic cholinergic receptors. The reversible binding of [3H]QNB to rat brain membranes was inhibited in a concentration dependent and saturable manner by both procaine and BAP, with Ki values of 4 x 10(-6) and 3 x 10(-7) M, respectively, and complete inhibition at 1 x 10(-5) M. Both procaine and BAP, although at much concentrations, inhibited the binding of [3H]methylcarbamylcholine in a concentration dependent manner, with Ki values of 5 x 10(-5) and 1 x 10(-5) M, respectively, and complete inhibition for both at 1 x 10(-3) M. Plots of the % irreversible inhibition of [3H]QNB, [3H]nicotine, and [3H]MCC vs [BAP] yielded Ki values of 7 x 10(-8), 1 x 10(-4), and 6 x 10(-5) M, respectively. In behavioral studies BAP was able to antagonize the QNB-induced hyperactivity in mice; however, BAP did not appear to alter nicotine-induced seizure activity or other behavioral effects in mice. A plot of the time course of inhibition by BAP for [3H]QNB binding revealed that the inhibition was almost complete within 10 min exposure at 37 degrees. The findings indicate that BAP is a useful affinity ligand for examining the biochemical and functional characteristics of brain cholinergic receptors, particularly the muscarinic which has an affinity near the nM concentration range.
authors.affiliation: Department of Pharmacology, University of Rochester Medical Center, NY 14642.
authors.forename: M
authors.initials: M
authors.lastname: Saraswati
authors.forename: M
authors.initials: M
authors.lastname: Hashmi
authors.forename: L G
authors.initials: LG
authors.lastname: Abood
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002217:Carbachol / Q000031:analogs & derivatives / Q000378:metabolism; D002729:Chloromercuribenzoates / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced; D008024:Ligands; D008623:Mercaptoethanol / Q000494:pharmacology; D015394:Molecular Structure; D009270:Naloxone / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism; D011343:Procaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy; D020245:p-Chloromercuribenzoic Acid
chemical_list: D002729:Chloromercuribenzoates; D008024:Ligands; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; C075347:4-bromoacetamidoprocaine; C053765:N-methylcarbamylcholine; D009270:Naloxone; D011343:Procaine; D020245:p-Chloromercuribenzoic Acid; D008623:Mercaptoethanol; D011813:Quinuclidinyl Benzilate; D009538:Nicotine; D002217:Carbachol