title: Effects of CI-1002 and CI-1017 on spontaneous synaptic activity and on the nicotinic acetylcholine receptor of Torpedo electric organ.
abstract: The effect of azepino[2,1-b]quinazoline 1,3-dichloro-6,7,8,9,10, 12-hexahydro-, mono-hydrochloride (CI-1002), a tacrine derivative, and 1-azabicyclo[2.2.1]heptan-3-one, O-[3-(methoxyphenyl)-2-propynyl]oxime [R-(Z)]-2-butenedioate (CI-1017), a muscarinic M(1) receptor agonist, on spontaneous synaptic activity was investigated by measuring amplitude, rise time, velocity of rising, half-width, and electrical charge of miniature endplate potentials (m.e.p.p.) recorded extracellularly in Torpedo electric organ fragments. The effect of CI-1002 and CI-1017 on the nicotinic acetylcholine receptor was investigated by measuring the current induced by acetylcholine in Xenopus laevis oocytes transplanted with membranes from Torpedo electric organ. CI-1002, at a concentration of 1 microM, altered the m.e.p.p. by increasing the amplitude (from 1.08+/-0.01 to 2.76+/-0.03 mV), rise time (from 0. 700+/-0.006 to 1.02+/-0.01 ms), rising rate (from 1.79+/-0.02 to 3. 45+/-0.05 mV/ms), half-width (from 0.990+/-0.008 to 2.40+/-0.02 ms), and electrical charge (from 304+/-4 to 784+/-11 mV s). CI-1017, at a concentration of 1 microM, altered the m.e.p.p. by decreasing the amplitude (from 1.08+/-0.01 to 0.650+/-0.007 mV), rise time (from 0. 700+/-0.006 to 0.530+/-0.007 ms), rising rate (from 1.79+/-0.02 to 1. 53+/-0.02 mV/ms), half-width (from 0.990+/-0.008 to 0.670+/-0.007 ms), and electrical charge (from 304+/-4 to 75+/-1 mV s). CI-1002 inhibited the acetylcholine-induced current of nicotinic acetylcholine receptors with an IC(50) of 3.4+/-0.3 microM. CI-1017 inhibited the acetylcholine-induced current of nicotinic acetylcholine receptors with an IC(50) of 0.8+/-0.1 microM. These results indicate that, although both drugs interacted negatively with nicotinic acetylcholine receptors, CI-1002 overcame this inhibition by recruiting more acetylcholine to build a quantum.
authors.affiliation: Laboratori de Neurobiologia Cellular i Molecular, Departament de Biologia Cellular i Anatomia Patològica, Hospital de Bellvitge, Universitat de Barcelona, Campus de Bellvitge, Pavelló de Govern, Feixa Llarga s/n E-08907, L'Hospitalet de Llobregat, SpainE
authors.forename: E
authors.initials: E
authors.lastname: Ros
authors.forename: J
authors.initials: J
authors.lastname: Aleu
authors.forename: J
authors.initials: J
authors.lastname: Marsal
authors.forename: C
authors.initials: C
authors.lastname: Solsona
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004557:Electric Organ / Q000187:drug effects*; D004594:Electrophysiology; D066298:In Vitro Techniques; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects; D010091:Oximes / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics; D013569:Synapses / Q000187:drug effects*; D014101:Torpedo / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D010091:Oximes; D011799:Quinazolines; D011978:Receptors, Nicotinic; C096405:PD 142505-0028; C092564:PD 142676