Biomaterial Database

Studies on RX 781094: a selective, potent and specific antagonist of alpha 2-adrenoceptors. 1983

J C Doxey, and A G Roach, and C F Smith

1 The selectivity and specificity of RX 781094 [2-(2-(1,4 benzodioxanyl))2-imidazoline HCl] for alpha-adrenoceptors have been examined in peripheral tissues. 2 In isolated tissue experiments RX 781094 was a competitive antagonist at prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of the rat (pA2 = 8.56) and mouse (pA2 = 7.93) vas deferens and on the parasympathetic nerve terminals of the guinea-pig ileum (pA2 = 8.55). 3 Although RX 781094 was also a competitive antagonist at the postjunctional alpha 1-adrenoceptors of the rat anococcygeus muscle (pA2 = 6.10) its affinity for these receptors was markedly less than that displayed for prejunctional sites. From pA2 values obtained in the rat vas deferens and anococcygeus muscle the calculated alpha 2/alpha 1-adrenoceptor selectivity ratio for RX 781094 was 288. 4 The rank order of alpha 2/alpha 1-adrenoceptor selectivities for the antagonists studied was RX 781094 greater than RS 21361 greater than yohimbine greater than piperoxan greater than phentolamine greater than WB 4101 greater than prazosin. 5 RX 781094 had extremely low affinity for beta-adrenoceptors, histamine receptors, cholinoceptors, 5-hydroxytryptamine and opiate receptors in vitro. 6 In pithed rats, intravenous administration of RX 781094 antagonized the prejunctional alpha 2-adrenoceptor agonist effects of clonidine and guanabenz on electrically-induced contractions of the vas deferens and anococcygeus muscle respectively. 7 In the vas deferens the rank order of alpha 2-adrenoceptor antagonist potencies was RX 781094 greater than phentolamine greater than piperoxan greater than yohimbine greater than RS 21361 greater than WB 4101. Only RX 781094, yohimbine and RS 21361 were active against guanabenz in the anococcygeus muscle. 8 In the pithed rat, RX 781094 preferentially antagonized the pressor responses evoked by postjunctional alpha 2-adrenoceptor activation by UK 14,304 although higher doses also inhibited the effects of phenylephrine and cirazoline at postjunctional alpha 1-adrenoceptors. 9 RX 781094 had little effect on the cardiovascular responses to 5-hydroxytryptramine, angiotensin II, histamine, acetylcholine and isoprenaline in pithed rats and rats anaesthetized with pentobarbitone. 10 These results demonstrate that RX 781094 is a potent and selective alpha 2-adrenoceptor antagonist with a high degree of specificity for these receptors.

UI	MeSH Term	Description	Entries
D007082	Ileum	The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
D008297	Male		Males
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011942	Receptors, Adrenergic, alpha	One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.	Adrenergic alpha-Receptor,Adrenergic alpha-Receptors,Receptors, alpha-Adrenergic,alpha-Adrenergic Receptor,alpha-Adrenergic Receptors,Receptor, Adrenergic, alpha,Adrenergic alpha Receptor,Adrenergic alpha Receptors,Receptor, alpha-Adrenergic,Receptors, alpha Adrenergic,alpha Adrenergic Receptor,alpha Adrenergic Receptors,alpha-Receptor, Adrenergic,alpha-Receptors, Adrenergic
D001794	Blood Pressure	PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.	Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D003000	Clonidine	An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.	Catapres,Catapresan,Catapressan,Chlophazolin,Clofelin,Clofenil,Clonidine Dihydrochloride,Clonidine Hydrochloride,Clonidine Monohydrobromide,Clonidine Monohydrochloride,Clopheline,Dixarit,Gemiton,Hemiton,Isoglaucon,Klofelin,Klofenil,M-5041T,ST-155,Dihydrochloride, Clonidine,Hydrochloride, Clonidine,M 5041T,M5041T,Monohydrobromide, Clonidine,Monohydrochloride, Clonidine,ST 155,ST155
D004147	Dioxins	A family of compounds that contain the 1,4-dioxin structure. Many specific dioxin derivatives are listed as CARCINOGENS; TERATOGENS; or MUTAGENS.	Dioxin
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response