BIOMAT Database Logo BIOMAT Database Logo

Characterization of a novel and potent 5-hydroxytryptamine1A receptor antagonist. 1991

L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
Department of Neurology, Stanford University Medical Center, CA 94305.

A series of pindolol derivatives (n = 7) was analyzed in radioligand binding, biochemical and behavioral studies. Three of these drugs (Compounds A, B, and C) are extremely potent (i.e., Ki values less than 1.0 nM) at 5-hydroxytryptamine1A (5-HT1A) sites labeled by [3H] 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Moreover, these drugs are selective in that they are approximately an order of magnitude less potent at beta-adrenergic receptors labeled by 3H-dihydroalprenolol (DHA). Compound A (N1-(bromoacetyl)-N8-[3-(4-indolyloxy)-2-hydroxypropyl]-(Z)-1,8-di amino-p- methane) is also significantly less potent at 10 other neurotransmitter receptor sites analyzed. In addition, Compound A (10(-10) M to 10(-3) M) has no effect on baseline forskolin-stimulated adenylate cycalse activity in rat hippocampus. By contrast, nanomolar concentrations of the drug significantly (p less than 0.01) reverse 8-OH-DPAT-induced inhibition of forskolin-stimulated activity. In behavioral studies. Compound A (0.5 mg/kg) alone has no effect on baseline measures of reciprocal forepaw treading in the rat. Pretreatment with Compound A, however, significantly (p less than 0.05) inhibits the reciprocal forepaw treading induced by 8-OH-DPAT. These data suggest that Compound A is a potent and selective antagonist of 5-HT1A receptors in the CNS.

UI MeSH Term Description Entries
D008297 Male Males
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
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
D011943 Receptors, Adrenergic, beta One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS. Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005576 Colforsin Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D000262 Adenylyl Cyclases Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP. Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
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
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D012702 Serotonin Antagonists Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS. 5-HT Antagonist,5-HT Antagonists,5-Hydroxytryptamine Antagonist,5-Hydroxytryptamine Antagonists,Antiserotonergic Agent,Antiserotonergic Agents,Serotonin Antagonist,Serotonin Blockader,Serotonin Blockaders,Serotonin Receptor Antagonist,Serotonin Receptor Blocker,Antagonists, 5-HT,Antagonists, 5-Hydroxytryptamine,Antagonists, Serotonin,Serotonin Receptor Antagonists,Serotonin Receptor Blockers,5 HT Antagonist,5 HT Antagonists,5 Hydroxytryptamine Antagonist,5 Hydroxytryptamine Antagonists,Agent, Antiserotonergic,Agents, Antiserotonergic,Antagonist, 5-HT,Antagonist, 5-Hydroxytryptamine,Antagonist, Serotonin,Antagonist, Serotonin Receptor,Antagonists, 5 HT,Antagonists, 5 Hydroxytryptamine,Antagonists, Serotonin Receptor,Blockader, Serotonin,Blockaders, Serotonin,Blocker, Serotonin Receptor,Blockers, Serotonin Receptor,Receptor Antagonist, Serotonin,Receptor Antagonists, Serotonin,Receptor Blocker, Serotonin,Receptor Blockers, Serotonin

Related Publications

L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
The pharmacological characterization of a novel selective 5-hydroxytryptamine1A receptor antagonist, NAD-299.
October 1997, The Journal of pharmacology and experimental therapeutics,
L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
Effects of pindobind 5-hydroxytryptamine1A (5-HT1A), a novel and potent 5-HT1A antagonist, on social and agonistic behaviour in male albino mice.
September 1993, Pharmacology, biochemistry, and behavior,
L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
Characterization of BU09059: a novel potent selective κ-receptor antagonist.
March 2014, ACS chemical neuroscience,
L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
Pharmacological characterization of recombinant human 5-hydroxytryptamine1A receptors using a novel antagonist radioligand, [3H]WAY-100635.
January 1997, Life sciences,
L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
Characterization of the aminomethylchroman derivative BAY x 3702 as a highly potent 5-hydroxytryptamine1A receptor agonist.
March 1998, The Journal of pharmacology and experimental therapeutics,
L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
Characterisation of the binding of [3H]WAY-100635, a novel 5-hydroxytryptamine1A receptor antagonist, to rat brain.
June 1995, Journal of neurochemistry,
L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
SUVN-502, a novel, potent, pure, and orally active 5-HT6 receptor antagonist: pharmacological, behavioral, and neurochemical characterization.
February 2019, Behavioural pharmacology,
L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
Antithrombotic activity of SR 46349, a novel, potent and selective 5-HT2 receptor antagonist.
March 1993, Thrombosis and haemostasis,
L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
GR127935: a potent and selective 5-HT1D receptor antagonist.
January 1996, Behavioural brain research,
L M Liau, and A J Sleight, and J Pitha, and S J Peroutka
Pharmacological characterization of RP 62203, a novel 5-hydroxytryptamine 5-HT2 receptor antagonist.
January 1992, British journal of pharmacology,
Copied contents to your clipboard!