Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/21379
Título: Novel tacrine derivatives that block neuronal calcium channels
Autor: de los Rios, C
Marco, JL
Carreiras, MDC
Chinchon, PM
Garcia, AG
Villarroya, M
Palavras-chave: Biochemistry & Molecular Biology
Chemistry, Medicinal
Chemistry, Organic
Data: 2002
Editora: PERGAMON-ELSEVIER SCIENCE LTD
Citação: BIOORGANIC & MEDICINAL CHEMISTRY. - Vol. 10, n. 6 (JUN 2002), p. 2077-2088
Resumo: 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.
URI: http://hdl.handle.net/10451/21379
ISSN: 0968-0896
Aparece nas colecções:FF - Produção Científica 2000-2009

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