HEAT hydrochloride

HEAT (BE2254) hydrochloride is a selective alpha 1 adrenergic receptor antagonist. HEAT hydrochloride, a phenethylamine derivative, shows pKis of 9, 9.1, and 8.57 for alpha 1a, alpha 1b and alpha 1c, respectively[1][2].

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Research Areas >> Neurological Disease

BE2254 inhibits (-)-noradrenaline-mediated increases in gluconeogenesis with K,sub>B of 0.74 nM[2]. The alpha-1 selective antagonist [125I]BE2254 is used to specifically label a single class of binding sites with a dissociation constant of 131.0 pM and a maximal binding capacity of 17.6 fmol/mg of protein. Catecholamines compete for [125I]BE2254 binding stereospecifically and with the characteristic alpha adrenergic potency series of (-)-epinephrine greater than (-)-norepinephrine much greater than (-)-isoproterenol. The alpha-1 selective antagonist prazosin (Kd=2.4 nM) is much more potent in competing for [125I]BE2254 binding than is the alpha-2 selective antagonist yohimbine (Kd=2900 nM)[3].

[1]. Chiu G, et al. Design and synthesis of an alpha1a-adrenergic receptor subtype-selective antagonist from BE2254. Chem Biol Drug Des. 2006;67(6):437-439.

[2]. McPherson GA, et al. A study of alpha 1-adrenoceptors in rat renal cortex: comparison of [3H]-prazosin binding with the alpha 1-adrenoceptor modulating gluconeogenesis under physiological conditions. Br J Pharmacol. 1982;77(1):177-184.

[3]. Tsujimoto G, et al. Alpha adrenergic receptors in the rabbit bladder base smooth muscle: alpha-1 adrenergic receptors mediate contractile responses. J Pharmacol Exp Ther. 1986;236(2):384-389.

MOLECULAR FORMULA :

C19-H21-N-O2.Cl-H

MOLECULAR WEIGHT :

331.87

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

650 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,231,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

22500 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,231,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

730 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,231,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

33 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,231,1982