92564-08-4

HA-1004 is an inhibitor of protein kinase G (PKG) and PKA (K_is = 1.4 and 2.3 μM, respectively). It also inhibits PKC and blocks intracellular calcium mobilization. HA-1004 induces relaxation of isolated rabbit aortic strips precontracted with histamine, serotonin , A23187 , angiotensin II , or prostaglandin F_2α (; EC₅₀s = 0.32-0.63 μM), as well as phenylephrine (Item Nos. 18619 | 17205) with or without calcium (EC₅₀s = 2.3 and 0.5 μM, respectively). It also inhibits histamine-induced bronchoconstriction in guinea pigs without affecting blood pressure when administered intratracheally at a dose of 0.1 mg per animal.

HA-1004 dihydrochloride is a selective inhibitor of PKA, which can inhibit lipolysis and induce vascular relaxation. HA-1004 dihydrochloride is also a dual inhibitor of cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein, and is involved in smooth muscle, second messenger, cyclic AMP and cyclic GMP regulation mechanisms. HA-1004 dihydrochloride is an antagonist for calcium, that can be used as a vasodilator to inhibit the contraction of rabbit aortic strips, or to antagonize ERK and tyrosine hydroxylase (TH) phosphorylation in morphine abstinence rat models[1][2][3].

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[1] Almela P, et al. Crosstalk between G protein-coupled receptors (GPCRs) and tyrosine kinase receptor (TXR) in the heart after morphine withdrawal. Front Pharmacol. 2013 Dec 27;4:164. DOI:10.3389/fphar.2013.00164
[2] Goodman HM, et al. The isoquinoline sulfonamide inhibitors of protein phosphorylation, H-7, H-8, and HA-1004, also inhibit RNA synthesis: studies on responses of adipose tissue to growth hormone. Endocrinology. 1990 Jan;126(1):441-50. DOI:10.1210/endo-126-1-441
[3] Ishikawa T, et al. Relaxation of vascular smooth muscle by HA-1004, an inhibitor of cyclic nucleotide-dependent protein kinase. J Pharmacol Exp Ther. 1985 Nov;235(2):495-9. PMID:2997436