Subissi A, Del Monte M
Department of Pharmacology, Laboratori Guidotti S.p.A., Pisa, Italy.
J Pharm Pharmacol. 1988 Apr;40(4):247-51. doi: 10.1111/j.2042-7158.1988.tb05237.x.
LG 30435 (N-methylmequitazine) was assayed in passive lung (PLA) and cutaneous (PCA) anaphylaxis in guinea-pigs and rats. At doses from 0.3 to 3 mumol kg-1 i.v., it produced a dose-dependent inhibition of guinea-pig PLA and of rat PCA and PLA, while the parent compound was ineffective or poorly effective up to 3 mumol kg-1. An attempt was made to elucidate the mechanism of LG 30435's action in these anaphylactic models, by means of various antagonists. It was tentatively concluded that different mechanisms are involved in the protective action of LG 30435 in each of the three models: histamine antagonism, possibly accompanied by an inhibition of the effects of peptido-leukotrienes in guinea-pig PLA; histamine antagonism in rat PCA and 5-hydroxytryptamine antagonism in rat PLA, possibly accompanied by a mast-cell stabilizing action in both cases. LG 30435 is devoid of smooth muscle relaxant effects on the airways and its demonstrated anticholinergic and anti-PAF effects do not appear to be involved in its antiallergic action.
对豚鼠和大鼠进行了被动肺过敏反应（PLA）和皮肤过敏反应（PCA）实验，以检测LG 30435（N - 甲基美喹他嗪）的效果。静脉注射剂量为0.3至3 μmol kg⁻¹时，它能剂量依赖性地抑制豚鼠的PLA以及大鼠的PCA和PLA，而母体化合物在高达3 μmol kg⁻¹时无效或效果不佳。通过使用各种拮抗剂，试图阐明LG 30435在这些过敏模型中的作用机制。初步得出结论，LG 30435在三种模型中的保护作用涉及不同机制：在豚鼠PLA中为组胺拮抗作用，可能伴有对肽白三烯作用的抑制；在大鼠PCA中为组胺拮抗作用，在大鼠PLA中为5 - 羟色胺拮抗作用，两种情况下可能都伴有肥大细胞稳定作用。LG 30435对气道平滑肌无舒张作用，其已证实的抗胆碱能和抗PAF作用似乎不参与其抗过敏作用。
