BMY 7378 (BMY-7378; BMY7378) dihydrochloride is a multi-target compound that inhibits α2C-adrenoceptor and α1D-adrenoceptor with pKi values of 6.54 and 8.2, respectively.

Physicochemical Properties

Molecular Formula	C22H33CL2N3O3
Molecular Weight	458.42
Exact Mass	457.189
Elemental Analysis	C, 57.64; H, 7.26; Cl, 15.47; N, 9.17; O, 10.47
CAS #	21102-95-4
Related CAS #	21102-94-3 (Free base); 21102-95-4 (HCl)
PubChem CID	210172
Appearance	Typically exists as White to off-white solid at room temperature
Boiling Point	585.6ºC at 760 mmHg
Melting Point	196.5-198.5 °C
Flash Point	307.9ºC
Vapour Pressure	1.07E-13mmHg at 25°C
LogP	4.071
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	30
Complexity	547
Defined Atom Stereocenter Count	0
SMILES	Cl[H].Cl[H].O=C1C([H])([H])C2(C([H])([H])C(N1C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])N(C3=C([H])C([H])=C([H])C([H])=C3OC([H])([H])[H])C([H])([H])C1([H])[H])=O)C([H])([H])C([H])([H])C([H])([H])C2([H])[H]
InChi Key	NIBOMXUDFLRHRV-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H31N3O3.2ClH/c1-28-19-7-3-2-6-18(19)24-13-10-23(11-14-24)12-15-25-20(26)16-22(17-21(25)27)8-4-5-9-22;;/h2-3,6-7H,4-5,8-17H2,1H3;2*1H
Chemical Name	8-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-8-azaspiro[4.5]decane-7,9-dione;dihydrochloride
Synonyms	BMY 7378; BMY-7378; 21102-95-4; BMY 7378 dihydrochloride; BMY 7378; 8-(2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl)-8-azaspiro[4.5]decane-7,9-dione dihydrochloride; BMY7378; 8-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-8-azaspiro[4.5]decane-7,9-dione;dihydrochloride; KC07KV8T5O; 1,1-Cyclopentanediacetimide, N-(2-(4-(o-methoxyphenyl)-1-piperazinyl)ethyl)-, dihydrochloride; BMY7378
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	5-HT1A ( pIC50 = 8.3 ); α1D-adrenoceptor ( pKi = 8.2 ); Dopamine D2 receptor ( pIC50 = 7.4 ); α2C-adrenoceptor ( pKi = 6.54 ); 5-HT1C ( pIC50 = 6.4 )
ln Vitro	In vitro activity: BMY 7378 exhibits selectivity for the alpha 1D-adrenoceptor subtype (pKi: hamster alpha 1b-adrenoceptor 6.2, human alpha 1b-adrenoceptor 7.2; bovine alpha 1c-adrenoceptor 6.1, human alpha 1c-adrenoceptor 6.6; rat alpha 1d-adrenoceptor 8.2, human alpha 1d-adrenoceptor 9.4) and exhibits a high affinity (pA2, 8.9) for rat aorta alpha 1-adrenoceptor][2].
ln Vivo	BMY 7378 (pA2 of 8.67) is approximately 100 times more potent than yohimbine (pA2 of 6.62) against contractions to noradrenaline in rat aorta. BMY 7378 (pA2 of 6.48) is approximately 10 times less potent than yohimbine (pA2 of 7.56) at antagonizing the contractile response to noradrenaline in human saphenous vein (α2C-adrenoceptor). BMY 7378 dose dependently (0.25-5 mg/kg s.c.) reduces the undetectable levels forepaw treading and head weaving induced by 8-OH-DPAT (0.75 mg/kg s.c.) in rats. BMY 7378 causes a marked and dose-dependent (0.01-1.0 mg/kg s.c.) decrease of 5-HT release in ventral hippocampus of the anaesthetized rat as detected by brain microdialysis in rats.
Enzyme Assay	BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8- azaspiro[4.5]decane-7,9-dione dihydrochloride), a 5-HT1A receptor partial agonist, also binds to alpha 1-adrenoceptors. Competition assays were performed using (+/-)-beta-([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone ([125I]HEAT), and membranes prepared from Rat-1 fibroblasts expressing hamster alpha 1b-, bovine alpha 1c-, or rat alpha 1d-adrenoceptor, or their respective human homologues. Results indicate that BMY 7378 is selective for the alpha 1D-adrenoceptor subtype (pKi: hamster alpha 1b-adrenoceptor 6.2 +/- 0.03, human alpha 1b-adrenoceptor 7.2 +/- 0.05; bovine alpha 1c-adrenoceptor 6.1 +/- 0.02, human alpha 1c-adrenoceptor 6.6 +/- 0.20; rat alpha 1d-adrenoceptor 8.2 +/- 0.06, human alpha 1d-adrenoceptor 9.4 +/- 0.05) and has high affinity (pA2, 8.9 +/- 0.1) for rat aorta alpha 1-adrenoceptor. [2]
Cell Assay	With a selective antagonist, the specific contribution of the alpha-1D adrenoceptor (AR) to vascular smooth muscle contraction has been assessed. BMY 7378 bound to membranes expressing the cloned rat alpha-1D AR with a > 100-fold higher affinity (K1 = 2 nM) than binding to either the cloned rat alpha-1A AR (Ki = 800 nM) or the hamster alpha-1B AR (Ki = 600 nM). BMY 7378 exhibited differential potency in inhibiting vascular smooth muscle contraction. In the rat aorta and iliac artery, BMY 7378 was a high-affinity antagonist, producing parallel shifts in the phenylephrine concentration-response curve. The dissociation constants for this compound by Schild analysis were 0.95 and 4 nM for the aorta and iliac artery, respectively. The slopes of these Schild plots were not significantly different from unity. BMY 7378 was a weak antagonist in the rat caudal, mesenteric resistance and renal arteries, with Schild slopes significantly < 1. With ribonuclease protection assays, alpha-1D mRNA was found in all blood vessels examined. These data suggest that (1) BMY 7378 is a selective alpha-1D AR antagonist that can be used in functional systems to assess the contribution of this receptor in vascular smooth muscle contraction; (2) the alpha-1D AR appears to play a major role in the contraction of the aorta and iliac artery; (3) despite the fact that the mRNA for the alpha-1D AR can be detected in the caudal, mesenteric resistance (4) and renal arteries, it does not appear to play a role in mediating contraction of these blood vessels; and (4) expression of alpha-1D mRNA in a particular artery does not ensure that this receptor is involved in regulating the contraction of that artery. [1]
Animal Protocol	Dissolved in 0.9% sodium chloride solution; 0.25-5 mg/kg; s.c. injection Rat
Toxicity/Toxicokinetics	mouse LD50 intraperitoneal 53600 ug/kg Journal of Medicinal Chemistry., 12(876), 1969
References	[1]. The specific contribution of the novel alpha-1D adrenoceptor to the contraction of vascular smooth muscle. J Pharmacol Exp Ther. 1995;275(3):1583-1589. [2]. BMY 7378 is a selective antagonist of the D subtype of alpha 1-adrenoceptors. Eur J Pharmacol. 1995;272(2-3):R5-R6.
Additional Infomation	Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.

Solubility Data

Solubility (In Vitro)	DMSO: ~92 mg/mL (~200.7 mM) Water: ~92 mg/mL (~200.7 mM) Ethanol: ~20 mg/mL (~43.6 mM)
Solubility (In Vivo)	Saline: 15 mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1814 mL	10.9070 mL	21.8141 mL
	5 mM	0.4363 mL	2.1814 mL	4.3628 mL
	10 mM	0.2181 mL	1.0907 mL	2.1814 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.