Twist E C, Mitchell S N, Corn T H, Campbell I C
Department of Neuroscience, Institute of Psychiatry, London, U.K.
Eur J Pharmacol. 1991 Apr 17;196(2):157-60. doi: 10.1016/0014-2999(91)90422-m.
As part of an investigation of ritanserin-induced receptor down-regulation, monoamine and metabolite levels in rat frontal cortex were measured following chronic ritanserin (2 mg/kg per day) or clorgyline (10 mg/kg per day) administration. Clorgyline increased 5-hydroxytryptamine (5-HT) by 83%, noradrenaline (NA) by 54%, and dopamine (DA) by 16% and decreased 5-hydroxyindoleacetic acid (5-HIAA) by 28%, homovanillic acid (HVA) by 57% and 3,4-dihydroxyphenylacetic acid (DOPAC) by 67%. All these changes were statistically significant (P less than 0.001) except for the increase in DA. Ritanserin increased 5-HT by 30%, NA by 33% and DA by 26% and decreased 5-HIAA by 22%, HVA by 23% and DOPAC by 40%; however, only the increases in 5-HT and NA reached statistical significance (P less than 0.05). Monoamine oxidase (MAO) activity in cortical homogenates was also measured following the chronic ritanserin and clorgyline regimens and also following ritanserin administration in vitro. Chronic clorgyline and ritanserin inhibited MAO activity by 60 and 39%, respectively. In vitro, ritanserin administration at concentrations of less than 10(-6) M had no effect on MAO activity but at doses higher than 10(-6) M, MAO activity was inhibited in a dose-dependent manner from 18 +/- 0.5% at 3 x 10(-6) M to 63 +/- 9% at 10(-4) M. Thus, ritanserin appears to act as an MAO inhibitor in addition to being a 5-HT2 antagonist and this may be related to its ability to induce 5-HT2 receptor down-regulation.
作为对利坦色林诱导受体下调的一项研究的一部分，在大鼠额叶皮质中，于长期给予利坦色林（每天2毫克/千克）或氯吉兰（每天10毫克/千克）后测量单胺和代谢物水平。氯吉兰使5-羟色胺（5-HT）增加83%，去甲肾上腺素（NA）增加54%，多巴胺（DA）增加16%，并使5-羟吲哚乙酸（5-HIAA）减少28%，高香草酸（HVA）减少57%，3,4-二羟基苯乙酸（DOPAC）减少67%。除了DA的增加外，所有这些变化均具有统计学显著性（P小于0.001）。利坦色林使5-HT增加30%，NA增加33%，DA增加26%，并使5-HIAA减少22%，HVA减少23%，DOPAC减少40%；然而，只有5-HT和NA的增加达到统计学显著性（P小于0.05）。在长期给予利坦色林和氯吉兰方案后以及在体外给予利坦色林后，还测量了皮质匀浆中的单胺氧化酶（MAO）活性。长期给予氯吉兰和利坦色林分别使MAO活性抑制60%和39%。在体外，浓度低于10(-6) M的利坦色林给药对MAO活性无影响，但在高于10(-6) M的剂量下，MAO活性以剂量依赖性方式受到抑制，从3×10(-6) M时的18±0.5%到10(-4) M时的63±9%。因此，利坦色林除作为5-HT2拮抗剂外，似乎还作为MAO抑制剂起作用，这可能与其诱导5-HT2受体下调的能力有关。
