systemically

Elgodipine significantly reduced the incidence and severity of exercise-induced angina pectoris systemically and was able to inhibit vascular smooth muscle proliferation through a mechanism independent of the expression of the transcription factors c-fos and c-jun. The Elgodipine-induced inhibition was voltage-dependent. Elgodipine is a potential compound for the treatment of angina pectoris.

VU0453595 is a M1 positive allosteric modulator (PAM).

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.

MK-8245 trifluoroacetate is a phenoxy piperidine isoxazole derivative functioning as a potent, liver-targeting stearoyl-CoA desaturase (SCD) inhibitor, demonstrating significant anti-diabetic and anti-dyslipidemic effects. It showcases high specificity and efficacy against SCD1 across various species, with IC50 values of 1 nM for human SCD1 and 3 nM for both rat and mouse SCD1. MK-8245's mechanism includes a tetrazole acetic acid moiety that facilitates liver-targeting through OATPs recognition. Its inhibition potency in rat hepatocyte assays (IC50 of 68 nM) surpasses that in HepG2 cell assays devoid of active OATPs (IC50 of ~1 μM), highlighting its liver specificity. Moreover, MK-8245 exhibits over 100,000-fold selectivity against Δ-5 and Δ-6 desaturases in comparative assays. In vivo studies reveal MK-8245's preferential liver distribution in mice, rats, dogs, and rhesus monkeys, underscoring its potential for minimizing adverse effects in non-target tissues. Additionally, its administration in eDIO mice before glucose challenges significantly improves glucose clearance, indicating its therapeutic promise in diabetes management.

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......

Meclocycline sulfosalicylate salt (Mecloderm), a tetracycline antibiotic, is used topically (i.e. for skin infections) as it is totally insoluble in water and may damage kidney and liver if given systemically.

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.

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).

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

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)

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

Meclocycline is a tetracycline antibiotic with broad antimicrobial activity. Meclocycline inhibits lactate dehydrogenase (LDH) release and cell toxicity induced by expression of htt-N63-148Q, a mutant form of the huntingtin gene, without altering htt-N63-148Q protein levels in PC12 cells.