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α1-Adrenoceptors are widely distributed, and are activated either by norepinephrine released from sympathetic nerve terminals or by epinephrine released from the adrenal medulla. Receptor activation mediates a variety of functions, including contraction of smooth muscle, cardiac stimulation, cellular proliferation/apoptosis and activation of hepatic gluconeogenesis and glycogenolysis. α1-Adrenoceptors are also widely distributed within the CNS, where their activation generally results in depolarization and increased neuronal firing rate. Most of the peripheral actions of α1-adrenoceptors are mediated through phosphatidylinositol turnover, while there is evidence for activation of adenylyl cyclase within the CNS.

Three distinct α1-adrenoceptor proteins have been cloned; after some confusion in nomenclature, it has now been established that these three recombinant α1-adrenoceptors, designated as α1a, α1b and α1d correspond to the pharmacologically defined α1a, α1b and α1d adrenoceptors in native tissues. Multiple slice variants of the α1a adrenoceptor have been identified; however, they appear to have identical pharmacological characteristics. The α1-adrenoceptor mediating contraction of several vascular and urogenital tissues has distinct pharmacology from the other 3 subtypes, and has been designated as the α1I adrenoceptor. This receptor has not been cloned; it now appears that the α1I adrenoceptor represents a discrete affinity state of the α1a adrenoceptor.

The subcellular location of expressed recombinant α1-adrenoceptors may be subtype dependent. Chloroethylclonidine, commonly used as a selective α1b antagonist for receptor subclassification, may be able to alkylate all α1-adrenoceptors, with its apparent selectivity for α1b versus α1a adrenoceptors, at least in cells expressing recombinant receptors, due to accessibility only to the α1b receptor. Evidence shows that it may be possible to design peptides which can selectively antagonize α1-adrenoceptor subtypes.

In most cases, the particular subtype involved in an α1-adrenoceptor mediated response has not yet been defined. This is due in part to the lack of subtype selective antagonists suitable for in vivo evaluation. Depending on the species and/or vascular bed, each α1-adrenoceptor subtype can contribute to vascular contraction. For example, contraction of the rat caudal artery is mediated by the α1a adreceptor, canine aorta by the α1b and rat aorta by the α1d adrenoceptor. The response to α1-adrenoceptor stimulation in many canine and human vessels has α1I pharmacology. Knockout of either α1a, α1b or α1d adrenoceptor significantly attenuates the pressor response to α1-adrenoceptor activation in the mouse. Contraction of prostatic and urethral smooth muscle appears to be mediated by the α1I adrenoceptor. α1-Adrenoceptor antagonists having selective affinity for α1a and α1I adrenoceptors, as well as antagonists having affinity for both α1a and α1d adrenoceptors, have been evaluated clinically for the treatment of benign prostatic hyperplasia. However, it appears that these drugs are not superior to the non-subtype selective α1-adrenoceptor antagonists, which have been proven to be effective for this indication.


The Table below contains accepted modulators and additional information. For a list of additional products, see the "Similar Products" section below.


Currently Accepted Name α1A α1B α1D
Alternate Name α1a, α1c
α1b α1d, α1a/d
Structural Information 466 aa (human) 517 aa (human) 573 aa (human)
Subtype Selective Agonist SKF-89748
Not Known
Not Known
Subtype Selective Antagonists (+)-Niguldipine
S-Methylurapidil (U101)
(±)-Cyclazosin (C247)
L-765,314 (L3040)

BMY 7378 (B134)
Receptor Selective Agonists Cirazoline (C223)
Methoxamine (M6524)
Phenylephrine (P6126)
Phenylephrine (P6126)
Methoxamine (M6524)
Phenylephrine (P6126)
Receptor Selective Antagonists Corynanthine
Prazosin (P7791)
Prazosin (P7791)
Prazosin (P7791)
Signal Transduction Mechanisms Gq/11 (increase IP3/DAG) Gq/11 (increase IP3/DAG)
Gq/11 (increase IP3/DAG)
Radioligands of Choice [3H]-Prazosin
Tissue Expression Heart, liver, CNS, urogenital smooth muscle Resistance vessels, spleen, kidney Aorta, bladder, CNS
Physiological Function Smooth muscle contraction, myocyte hypertrophy Smooth muscle contraction, CNS stimulation
Smooth muscle contraction, locomotor activity
Disease Relevance BPH, stress incontinence
Not Known
Overactive bladder



A-61603: N-[5-(4,5-Dihydro-1H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulfonamide hydrobromide
BMY 7378: 8-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-8-azasprio[4.5]decane-7,9-dione
HEAT: 2-(β-4-Hydroxyphenyl)ethylaminomethyltetralone
L-762,459: (±)-1-(3-{[5-Carbamoyl-2-{2-[(4-hydroxy-3-iodobenzimidoyl)-amino]-ethoxy-methyl}-6-methyl-4-(4-nitrophenyl)-1,4-dihydropyridine-4-carboxylic acid methyl ester
L-765,314: 4-Amino-2-[4-[1-(benzyloxycarbonyl)-2(S)-[[(1,1-dimethylethyl)amino]carbonyl]-piperazinyl]-6,7-dimethoxyquinazoline
RS-17053: (N-[2-(2-Cyclopropylmethoxyphenoxy)ethyl]-5-chloro-α,α-dimethyl-1H-indole-3-ethanamine
SKF-89748: 1,2,3,4-Tetrahydro-8-methoxy-5-(methylthio)-2-naphthalenamine


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