systemically

VU0453595 是有效的、高选择性的、全身活性的M1正变构调节剂 (PAM, EC50=2140 nM)，在精神分裂症方面有研究价值。

Elgodipine 显著降低了运动诱导的心绞痛系统的发生率和严重程度，能够通过独立于转录因子c-fos 和c-jun 表达的机制抑制血管平滑肌增殖。 Elgodipine 诱导的抑制是电压依赖性的。Elgodipine 是治疗心绞痛的潜在化合物。

Votoplam HCl(沃妥扑兰盐酸盐)是Votoplam的盐酸盐形式。Votoplam是一种全身作用的基因剪接调节剂，能够下调亨廷顿蛋白(huntingtin protein)的水平，主要用于抑制亨廷顿病(HD)。

Meclocycline sulfosalicylate salt (Mecloderm) 是一种具有广谱抗菌活性的四环素抗生素，可预防皮肤细菌感染。

Betamethasone 17-Propionate 在实验中主要是探讨其对大鼠内毒素诱导的葡萄膜炎的治疗潜力。通过滴眼和全身给药的方式，该化合物能在一定剂量（全身给药时为 1 mg kg）下抑制细胞在房水中的渗入，尽管其效果相比其他化合物较弱。在体外实验中，Betamethasone 17-Propionate 对大鼠腹膜渗出细胞中的白细胞介素-8（IL-8）的抑制作用也不如倍他米松。研究还发现，当与倍他米松二丙酸酯共同使用时，两者的联合效应可能减弱对细胞浸润和IL-1β基因表达的抑制。

AZD-9164，一种muscarinic M3 receptor antagonist，被开发用于治疗慢性阻塞性肺病（COPD）。AZD-9164旨在通过改善肺功能的幅度和持久性而不增加系统性不良事件，可能超越tiotropium的治疗指数。

JNJ-40068782 is a potent, selective and systemically active positive allosteric modulator of the mGlu2 receptor.

LY 215490 is a selective, competitive and systemically active antagonist of AMPA receptor. LY 215490 has neuroprotective effect against focal ischaemia in a model of permanent MCA occlusion in the rat.

LY 274614 is a structurally novel systemically active competitive NMDA receptor antagonist.

Methylatropine is an antagonist of muscarinic acetylcholine receptors (IC50= <0.1 nM in a radioligand binding assay using isolated porcine brain membranes) and a derivative of atropine .1,2It reduces acetylcholine-induced decreases in blood pressure in rats when administered intravenously with an ED50value of 5.5 μg/kg.2Methylatropine reduces salivation, induces mydriasis, and increases heart rate in dogs.3 1.Schmeller, T., Sporer, F., Sauerwein, M., et al.Binding of tropane alkaloids to nicotinic and muscarinic acetylcholine receptorsPharmazie50(7)493-495(1995) 2.Brezenoff, H.E., Xiao, Y.-F., and Vargas, H.A comparison of the central and peripheral antimuscarinic effects of atropine and methylatropine injected systemically and into the cerebral ventriclesLife Sci.42(8)905-911(1988) 3.Albanus, L.Central and peripheral effects of anticholinergic compoundsActa Pharmacol. Toxicol. (Copenh)28(4)305-326(1970)

MK-8245 trifluoroacetate is a liver-targeting inhibitor of stearoyl-CoA desaturase (SCD) with IC50 of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1, with anti-diabetic and anti-dyslipidemic efficacy. IC50 value: 1 nM (hSCD1) Target: SCD1 in vitro: MK-8245, a phenoxy piperidine isoxazole derivative, has been identified as a potent and liver-specific SCD inhibitor. It contains a tetrazole acetic acid moiety, which is the key molecule for OATPs recognition and liver-targeting. MK-8245 displays similar potencies against human, rat and mouse SCD1 with IC50 values of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1. MK-8245 exhibits a significant SCD inhibition in the rat hepatocyte assay which contains functional, active OATPs with IC50 of 68 nM, while being only weakly active in the HepG2 cell assay which is devoid of active OATPs with IC50 of ~1 μM. MK-8245 displays highly selective activity for the Δ-5 and Δ-6 desaturases (i.e., >100000 μM vs rat and human Δ5D and Δ6D as assessed in the HepG assay. in vivo: Administration of MK-8245 at 10 mg kg in mice exhibits a tissue distribution profile concentrated in the liver. It shows a liver-to-Harderian gland ratio of 21, suggesting a high degree of liver-targeting compared to a systemically distributed compound with liver-to-Harderian gland ratio of 1.5. Oral dosing of MK-8245 in mice, rats, dogs, and rhesus monkeys demonstrates that MK-8245 is distributed mainly to the liver, with low exposure in tissues associated with potential adverse events. The liver-to-skin ratios are >30:1 in all four species. Administration of MK-8245 to eDIO mice before the glucose challenge improves glucose clearance in a dose-dependent manner with ED50 of 7 mg kg.

Clocinnamox mesylate is a systemically active, irreversibleμ-opioid receptor antagonist (apparent Kivalues are 0.7, 1.9 and 5.7 nM for mouseμ,δandκreceptors respectively).

AS1940477 is p38 MAPK inhibitor. AS1940477 inhibited the enzymatic activity of recombinant p38α and β isoforms but showed no effect against other 100 protein kinases including p38γ and δ isoforms. In human peripheral blood mononuclear cells, AS1940477 inhibited lipopolysaccharide (LPS)- or phytohemagglutinin A (PHA)-induced production of proinflammatory cytokines, including TNFα, IL-1β, and IL-6 at low concentrations (LPS TNFα, IC(50)=0.45n M; PHA TNFα, IC(50)=0.40 nM). In addition, equivalent concentrations of AS1940477 that inhibited cytokine production also inhibited TNFα- and IL-1 β-induced production of IL-6, PGE(2), and MMP-3 in human synovial stromal cells. AS1940477 was also found to potently inhibit TNF production in whole blood (IC(50)=12 nM) and effectively inhibited TNFα production induced by systemically administered LPS in rats at less than 0.1mg kg (ED(50)=0.053 mg kg) with an anti-inflammatory effect lasting for 20h after oral administration. Overall, this stu......

LY2934747 is a novel, potent, and systemically bioavailable mGlu2 3 receptor agonist, exhibiting both antipsychotic and analgesic properties in vivo.

Clencyclohexerol is an analog of clenbuterol. β-Adrenoceptor agonists, including clenbuterol, modulate protein synthesis and degradation and have therapeutic potential in muscle wasting disorders. β-adrenoceptor agonists have deleterious cardiovascular side effects when used systemically and at high concentrations.