Biomaterial Database

Neuroendocrine evidence for antagonism of serotonin and dopamine receptors by olanzapine (LY170053), an antipsychotic drug candidate. 1992

R W Fuller, and H D Snoddy

Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.

Olanzapine, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-B] [1,5]benzodiazepine (LY170053), antagonized the quipazine-induced elevation of serum corticosterone concentration in rats with an ED50 value of 0.57 mg/kg i.p. LY170053 was less potent in antagonizing the pergolide-induced elevation of serum corticosterone concentration in rats, and increases in corticosterone elicited by olanzapine alone at higher doses complicated the precise estimate of an ED50 value, which was approximately 3 mg/kg. These relative potencies in blocking quipazine and pergolide effects are taken as indices of antagonism of serotonin 5HT2 and of dopamine D2 receptors, respectively. Olanzapine is more potent than clozapine in blocking 5HT2 and D2 receptors, and its ability to block these receptors supports its possible usefulness as an antipsychotic drug.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009490	Neurosecretory Systems	A system of NEURONS that has the specialized function to produce and secrete HORMONES, and that constitutes, in whole or in part, an ENDOCRINE SYSTEM or organ.	Neuroendocrine System,Neuroendocrine Systems,Neurosecretory System,System, Neuroendocrine,System, Neurosecretory,Systems, Neuroendocrine,Systems, Neurosecretory
D010479	Pergolide	A long-acting dopamine agonist which has been used to treat PARKINSON DISEASE and HYPERPROLACTINEMIA but withdrawn from some markets due to potential for HEART VALVE DISEASES.	Celance,LY-127,809,LY-127809,Parkotil,Pergolide Mesylate,Permax,Pharken,LY127,809,LY127809,Mesylate, Pergolide
D010890	Pirenzepine	An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.	Gastrotsepin,Gastrozepin,L-S 519,LS-519,Piren-Basan,Pirenzepin,Pirenzepin Von Ct,Pirenzepin-Ratiopharm,Pirenzepine Dihydrochloride,Pyrenzepine,Ulcoprotect,Ulgescum,Dihydrochloride, Pirenzepine,LS 519,LS519,Piren Basan,Pirenzepin Ratiopharm,Von Ct, Pirenzepin
D011814	Quipazine	A pharmacologic congener of serotonin that contracts smooth muscle and has actions similar to those of tricyclic antidepressants. It has been proposed as an oxytocic.	2-(1-Piperazinyl)quinoline,MA-1291,Quipazine Hydrochloride,Quipazine Maleate,Quipazine Maleate (1:1),MA 1291,MA1291
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
D003024	Clozapine	A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.	Clozaril,Leponex
D003345	Corticosterone	An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)
D004353	Drug Evaluation, Preclinical	Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.	Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D000077152	Olanzapine	A benzodiazepine derivative that binds SEROTONIN RECEPTORS; MUSCARINIC RECEPTORS; HISTAMINE H1 RECEPTORS; ADRENERGIC ALPHA-1 RECEPTORS; and DOPAMINE RECEPTORS. It is an antipsychotic agent used in the treatment of SCHIZOPHRENIA; BIPOLAR DISORDER; and MAJOR DEPRESSIVE DISORDER; it may also reduce nausea and vomiting in patients undergoing chemotherapy.	2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno(2,3-b)(1,5)benzodiazepine,LY 170053,LY-170052,Olanzapine Pamoate,Zolafren,Zyprexa,LY 170052,LY170052