Biomaterial Database

Structure-activity relationships of clonidine- and tolazoline-like compounds at histamine and alpha-adrenoceptor sites. 1980

E Malta, and J S Ong, and C Raper, and P E Tawa, and G N Vaughan

1 Thirty clonidine- and tolazoline-like compounds with differing phenyl ring substituents were tested for agonistic actions at histamine H1-receptors (guinea-pig ileum), histamine H2-receptors (guinea-pig driven right ventricular strips), post-junctional alpha-adrenoceptors (rat desheathed was deferens) and pre-junctional alpha-adrenoceptors (inhibition of sympathetic stimulation in guinea-pig driven left atria). 2 All compounds were inactive at histamine H1-receptors, while 21 of the 30 compounds displayed varying stimulant activity at H2-receptors. 3 At post-junctional alpha-receptors all 30 compounds produced stimulant actions, whereas at prejunctional alpha-receptors the compounds displayed either agonistic or antagonistic actions. 4 Thus structure-activity-relationships (SAR) could only be validated for histamine H2- and post-junctional alpha-receptor effects. These studies show that the most potent compounds are those with 2,6-phenyl substituents in which rotation is restricted so that the two rings are aplanar. Electronic effects of the substituents have a greater influence on activity at H2- than at alpha-receptors. 5 The major difference in SAR involves the influence of substituents in the 3, 4 or 5 positions on the phenyl ring. The presence of these substituents abolish significant activity at H2-receptors, while alpha-receptor stimulant activity is retained.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D011941	Receptors, Adrenergic	Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction.	Adrenergic Receptors,Adrenoceptor,Adrenoceptors,Norepinephrine Receptor,Receptors, Epinephrine,Receptors, Norepinephrine,Adrenergic Receptor,Epinephrine Receptors,Norepinephrine Receptors,Receptor, Adrenergic,Receptor, Norepinephrine
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
D011968	Receptors, Histamine	Cell-surface proteins that bind histamine and trigger intracellular changes influencing the behavior of cells. Histamine receptors are widespread in the central nervous system and in peripheral tissues. Three types have been recognized and designated H1, H2, and H3. They differ in pharmacology, distribution, and mode of action.	Histamine Binding Sites,Histamine Receptors,Histamine Receptor,Binding Sites, Histamine,Receptor, Histamine,Sites, Histamine Binding
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
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014043	Tolazoline	A vasodilator that apparently has direct actions on blood vessels and also increases cardiac output. Tolazoline can interact to some degree with histamine, adrenergic, and cholinergic receptors, but the mechanisms of its therapeutic effects are not clear. It is used in treatment of persistent pulmonary hypertension of the newborn.	Benzalolin,Divascol,Pridazole,Priscol,Priscoline,Tolazoline Hydrochloride,Tolazoline Monohydrochloride
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus