Publication
Novel tacrine derivatives that block neuronal calcium channels
| dc.contributor.author | de los Rios, C | |
| dc.contributor.author | Marco, JL | |
| dc.contributor.author | Carreiras, MDC | |
| dc.contributor.author | Chinchon, PM | |
| dc.contributor.author | Garcia, AG | |
| dc.contributor.author | Villarroya, M | |
| dc.date.accessioned | 2015-12-30T10:18:02Z | |
| dc.date.available | 2015-12-30T10:18:02Z | |
| dc.date.issued | 2002 | |
| dc.description.abstract | A new series of tacrine (9-amino-1,2,3,4-tetrahydroacridine) derivatives were synthesized and their effects on Ca-45 (2+) entry into bovine adrenal chromaffin cells stimulated with dimethylphenylpiperazinium (DMPP) or K+, studied. At 3 PM, compound 1 did not affect Ca-45(2+) uptake evoked by DMPP. Compounds 14, 15 and 17 inhibited the effects of DMPP by 30%. Compounds 3, 9 and tacrine blocked the DMPP signal by about 50%. Compounds 5 and 12 were the most potent blockers of DMPP-stimulated (45)Ca2(+) entry (90%); the rest of the compounds inhibited the effects of DMPP by 70-80%. Compounds 1, 3, 4, 8, 10, If, 13, 16, 17 and tacrine inhibited Ca-45(2+) Uptake induced by K+ about 20%. Compounds 6. 14 and 15 inhibited the K+ effects by 10% or less. Compounds 7, 9, 12 and 18 blocked the K+ signal by 30% and, finally, compounds 2 and 5 inhibited the K+-induced Ca-45(2+) entry by 50%, None of the new compounds was as effective as diltiazem (IC50 0.03 muM) in causing relaxation of the rat aorta precontracted with 35 mM K+; the most potent was compound 7(IC50 = 0.3 muM). Compounds 5, 6, 8, 9, 10 and 13 had IC(50)s around 10 muM and compounds 3, 4, 11 and 12 around 20 muM. Blockade of Ca2+ entry through neuronal voltage-dependent Ca2+ channels, without concomitant blockade of vascular Ca2+ channels, suggests that some of these compounds might exhibit neuroprotectant effects but not undesirable hemodynamic effects. (C) 2002 Elsevier Science Ltd. All rights reserved. | |
| dc.format | application/pdf | |
| dc.identifier.citation | BIOORGANIC & MEDICINAL CHEMISTRY. - Vol. 10, n. 6 (JUN 2002), p. 2077-2088 | |
| dc.identifier.issn | 0968-0896 | |
| dc.identifier.uri | http://hdl.handle.net/10451/21379 | |
| dc.language.iso | eng | |
| dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | |
| dc.subject | Biochemistry & Molecular Biology | |
| dc.subject | Chemistry, Medicinal | |
| dc.subject | Chemistry, Organic | |
| dc.title | Novel tacrine derivatives that block neuronal calcium channels | |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 2088 | por |
| oaire.citation.startPage | 2077 | por |
| oaire.citation.title | BIOORGANIC & MEDICINAL CHEMISTRY | por |
| oaire.citation.volume | Vol. 10 | por |
| rcaap.rights | restrictedAccess | |
| rcaap.type | article |