Kanda T, Tashiro T, Kuwana Y, Jenner P
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co Ltd, Shizuoka, Japan.
Neuroreport. 1998 Aug 24;9(12):2857-60. doi: 10.1097/00001756-199808240-00032.
Both adenosine A1 and A2 receptor populations are located in the striatum and can modify locomotor activity, and they may form a therapeutic target for Parkinson's disease (PD). Administration of the selective adenosine A2A antagonist (E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-pu rine-2,6-dione (KW-6002) to MPTP-treated common marmosets increased locomotor activity. In contrast, administration of the selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxantine (DPCPX) had no effect on locomotion. Administration of the adenosine A2A receptor agonist 2-[p-[2-(2-aminoethylamino) carbonylethyl] phenethyl amino]-5'-N-ethylcarboxamidoadenosine (APEC) dose dependently suppressed basal locomotor activity. A minimally effective dose of APEC (0.62 mg/kg, i.p) completely reversed the increase in locomotor activity produced by administration of KW-6002. The adenosine A2A receptor appears to be an important target for the treatment of basal ganglia disorders, particularly PD.
腺苷A1和A2受体群体均位于纹状体中,且能够改变运动活性,它们可能构成帕金森病(PD)的一个治疗靶点。向经1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)处理的普通狨猴施用选择性腺苷A2A拮抗剂(E)-1,3-二乙基-8-(3,4-二甲氧基苯乙烯基)-7-甲基-3,7-二氢-1H-嘌呤-2,6-二酮(KW-6002)可增加运动活性。相比之下,施用选择性A1受体拮抗剂1,3-二丙基-8-环戊基黄嘌呤(DPCPX)对运动没有影响。施用腺苷A2A受体激动剂2-[对-[2-(2-氨基乙基氨基)羰基乙基]苯乙氨基]-5'-N-乙基羧酰胺腺苷(APEC)可剂量依赖性地抑制基础运动活性。最低有效剂量的APEC(0.62mg/kg,腹腔注射)完全逆转了施用KW-6002所产生的运动活性增加。腺苷A2A受体似乎是治疗基底神经节疾病尤其是帕金森病的一个重要靶点。