Biomaterial Database

Evidence that SK & F 104078 does not differentiate between pre- and postjunctional alpha 2-adrenoceptors. 1988

S Connaughton, and J R Docherty

Department of Clinical Pharmacology, Royal College of Surgeons, Dublin, Ireland.

We have investigated the proposed postjunctional selectivity of the alpha 2-adrenoceptor antagonist SK & F 104078 employing the pithed rat, rat isolated atrium and human saphenous vein preparations. In the pithed rat, SK & F 104078 (5 mg kg-1) produced a 20-fold shift in the prejunctional ID50 (concentration of agonist producing 50% inhibition of the cardioacceleration to a single stimulus) and a 3-fold shift in the postjunctional ED50 (concentration producing 50% of maximum rise in diastolic blood pressure) of the alpha 2-adrenoceptor agonist xylazine. However, the alpha 2-adrenoceptor antagonist yohimbine also showed apparent selectivity for prejunctional receptors in the pitched rat. In the rat isolated atrium, yohimbine was approximately 10 times more potent than SK & F 104078 at enhancing the stimulation-evoked release of tritium in tissues preincubated with (3H)-noradrenaline. In the human saphenous vein, yohimbine and SK & F 104078 had pA2 values of 7.40 and 6.33, respectively, against contractions to noradrenaline, so that yohimbine was again approximately ten times more potent than SK & F 104078. In conclusion, SK & F 104078 behaved like yohimbine in its relative potencies at pre- and postjunctional alpha 2-adrenoceptors both in vivo and in vitro, so that we fail to find any selectivity of SK & F 104078 for postjunctional alpha 2-adrenoceptors.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
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
D003655	Decerebrate State	A condition characterized by abnormal posturing of the limbs that is associated with injury to the brainstem. This may occur as a clinical manifestation or induced experimentally in animals. The extensor reflexes are exaggerated leading to rigid extension of the limbs accompanied by hyperreflexia and opisthotonus. This condition is usually caused by lesions which occur in the region of the brainstem that lies between the red nuclei and the vestibular nuclei. In contrast, decorticate rigidity is characterized by flexion of the elbows and wrists with extension of the legs and feet. The causative lesion for this condition is located above the red nuclei and usually consists of diffuse cerebral damage. (From Adams et al., Principles of Neurology, 6th ed, p358)	Decerebrate Posturing,Decorticate Rigidity,Decorticate State,Rigidity, Decerebrate,Rigidity, Decorticate,Decerebrate Posturings,Decerebrate Rigidity,Decerebrate States,Decorticate Rigidities,Decorticate States,Posturing, Decerebrate,Posturings, Decerebrate,Rigidities, Decorticate,State, Decerebrate,States, Decerebrate
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000317	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.	Adrenergic alpha-Receptor Blockaders,alpha-Adrenergic Blocking Agents,alpha-Adrenergic Receptor Blockaders,alpha-Blockers, Adrenergic,Adrenergic alpha-Blockers,alpha-Adrenergic Antagonists,alpha-Adrenergic Blockers,Adrenergic alpha Antagonists,Adrenergic alpha Blockers,Adrenergic alpha Receptor Blockaders,Agents, alpha-Adrenergic Blocking,Antagonists, alpha-Adrenergic,Blockaders, Adrenergic alpha-Receptor,Blockaders, alpha-Adrenergic Receptor,Blockers, alpha-Adrenergic,Blocking Agents, alpha-Adrenergic,Receptor Blockaders, alpha-Adrenergic,alpha Adrenergic Antagonists,alpha Adrenergic Blockers,alpha Adrenergic Blocking Agents,alpha Adrenergic Receptor Blockaders,alpha Blockers, Adrenergic,alpha-Antagonists, Adrenergic,alpha-Receptor Blockaders, Adrenergic
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults