1-ヒドラジノフタラジン塩酸塩 化学特性,用途語,生産方法
外観
白色の結晶性の粉末(JP法)
溶解性
水にやや溶けやすく、エタノールに溶けにくい。
解説
1-hydrazinophthalazine monohydrochloride．C8H8N4HCl(196.64)．ヒドララジン塩酸塩, 1-クロロフタラジンにヒドラジンヒドラートを反応させると得られる．塩酸塩は分解点273 ℃．λmax 211，240，260，304，315 nm(水)．水に可溶，エタノールに難溶．血管の拡張による血圧低下作用を有し，抗高血圧症薬として使用される．種々の副作用を伴うので，長期投与には注意を要する．LD50 34 mg/kg(ラット，静注)．森北出版「化学辞典（第2版）
用途
降圧剤?血管拡張剤
用途
有機合成原料。
効能
血圧降下薬
商品名
アプレゾリン (サンファーマ); アプレゾリン (サンファーマ)
使用上の注意
アルゴン封入
説明
Hydralazine is an orally bioavailable vasodilator and antihypertensive agent. It decreases DNA methylation in Jurkat cells at a concentration of 10 μM and inhibits extracellular and intracellular production of reactive oxygen species (ROS) in rat macrophages activated by phorbol 12-myristate 13-acetate (PMA; ) at a concentration of 100 μM. Hydralazine (100 μM) also decreases nitric oxide production and mRNA expression of inducible nitric oxide synthase (iNOS) in rat macrophages activated by LPS (Item Nos.
19660|
19661|
19662) and interferon-γ (IFN-γ). It reduces contraction of rat aortic arterial strips induced by potassium and norepinephrine (; IC
50s = 2.2 and 3.06 mM, respectively). Hydralazine (2.6 mg/kg) lowers mean arterial blood pressure (MAP) by 41.76% in conscious rats. Formulations containing hydralazine have been used in the treatment of high blood pressure and heart failure.
化学的特性
White Crystalline Solid
使用
Hydralazine hydrochloride has been used:
- as a vasodilator to study its effects on hypertension in T-cell frequencies in juvenile rats
- as a semicarbazide-sensitive amine oxidase (SSAO) inhibitor to study its effects on myocardial ischemia-reperfusion (I/R) injury
- as a vasodilator to study its effects on insulin secretion and glucose tolerance
定義
ChEBI: The hydrochloride salt of hydralazine; a direct-acting vasodilator that is used as an antihypertensive agent.
一般的な説明
Hydralazine hydrochloride,1-hydrazinophthalazine monohydrochloride(Apresoline hydrochloride), originated from the work of achemist attempting to produce some unusual chemicalcompounds and from the observation that this compoundhad antihypertensive properties. It occurs as yellow crystalsand is soluble in water to the extent of about 3%. A 2%aqueous solution has a pH of 3.5 to 4.5.
接触アレルゲン
Hydralazine is a hydrazine derivative used as a antihypertensive
drug. Skin rashes have been described during
treatment. Exposure occurs mainly in the pharmaceutical
industry. Cross-sensitivity is frequent with hydrazine,
which is considered to be a potent sensitizer.
作用機序
The only drug in this group, hydralazine, does not fit neatly into the other mechanistic classes, in part because its
mechanism of action is not entirely clear. It appears to have multiple, direct effects on the VSM. Hydralazine, a
phthalazine-substituted hydrazine antihypertensive drug with a pKa of 7.3, is highly specific for arterial vessels,
producing its vasodilation by a couple of different mechanisms. First, it causes smooth muscle hyperpolarization, quite
likely through the opening of K+
channels. Activation therefore increases the efflux of potassium ions from the cells,
causing hyperpolarization of VSM cells and, thus, prolonging the opening of the potassium channel and sustaining a
greater vasodilation on arterioles than on veins. It also may inhibit the second messenger, IP3-induced release of
calcium from the smooth muscle sarcoplasmic reticulum (the PIP2 signal transduction pathway). Finally,
hydralazine stimulates the formation of NO by the vascular endothelium, leading to cGMP-mediated vasodilation. The arterial vasodilator action of hydralazine reduces systemic vascular resistance and arterial pressure.
Diastolic blood pressure usually is decreased more than systolic pressure is. The hydralazine-induced decrease in
blood pressure and peripheral resistance causes a reflex response, which is accompanied by increased heart rate,
cardiac output, stroke volume, and an increase in plasma renin activity. It has no direct effect on the heart. This
reflex response could offset the hypotensive effect of arteriolar dilation, limiting its antihypertensive effectiveness.
Hydralazine also causes sodium and water retention and expansion of plasma volume, which could develop tolerance
to its antihypertensive effect during prolonged therapy. Thus, coadministration of a diuretic improves the therapeutic
outcome.
臨床応用
Hydralazine hydrochloride is useful in the treatment ofmoderate-to-severe hypertension. It is often used in conjunctionwith less potent antihypertensive agents, becauseside effects occur frequently when it is used alone in adequatedoses. In combinations, it can be used in lower andsafer doses. Its action appears to be centered on the smoothmuscle of the vascular walls, with a decrease in peripheralresistance to blood flow. This results in increased bloodflow through the peripheral blood vessels. It also has theunique property of increasing renal blood flow, an importantconsideration in patients with renal insufficiency.Hydralazine hydrochloride acts on vascular smooth muscleto cause relaxation. Its mechanism of action is unclear. Itinterferes with Ca2
+ entry andCa2
+release from intracellularstores and reportedly causes activation of guanylate cyclase,resulting in increased levels of cGMP. All of thesebiochemical events can cause vasodilation.
薬物相互作用
The coadministration of diuretics and other hypotensive drugs may have a synergistic effect, resulting in a marked
decrease in blood pressure.
純化方法
It crystallises from MeOH and has m 172-173o(dec). [Druey et al. Helv Chim Acta 34 195 1951, Beilstein 25 III/IV 4552.] It is an antihypertensive.
1-ヒドラジノフタラジン塩酸塩 上流と下流の製品情報
原材料
準備製品