Biomaterial Database

Vascular and cardiac effects of alpha-methyl-5-HT and DOI are mediated by different 5-HT receptors in the pithed rat. 1993

K Chaouche-Teyara, and B Fournier, and M Safar, and H Dabiré

INSERM U 337, Faculté de Médecine Broussais Hôtel-Dieu, Paris, France.

In pithed rats, alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) increased blood pressure and heart rate, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) almost exclusively increased blood pressure and 1-(3-chlorophenyl)piperazine (mCPP), heart rate. The maximal responses relative to 5-HT indicate that alpha-methyl-5-HT may be a full agonist at vascular and cardiac 5-HT receptors, DOI a partial agonist at both receptors and mCPP a full agonist at cardiac 5-HT receptors but a partial agonist at vascular 5-HT receptors. The alpha 1-adrenoceptor antagonist, 2-[2-[4(o-methoxyphenyl)-piperazine-1-yl]-ethyl]4,4-dimethyl -1,3(2H-4H) isoquinolinedione (AR-C 239), did not change the pressor and tachycardiac effects of alpha-methyl-5-HT and DOI, excluding the participation of alpha 1-adrenoceptors. 4-Isopropyl-7-methyl-9-(2-hydroxy-1-methylpropoxycarbonyl) 4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline (LY 53857), spiperone and ketanserin but not propranolol antagonised the pressor effect of alpha-methyl-5-HT, indicating a preferential participation of 5-HT2 receptors although an implication of 5-HT1C receptors could not be ruled out. Spiperone, spiperone plus propranolol, LY 53857, ketanserin and propranolol antagonised the pressor effects of DOI suggesting the stimulation of both 5-HT2 and 5-HT1C receptors. Propranolol and spiperone plus propranolol suppressed the weak increase in heart rate induced by DOI, indicating the stimulation of 5-HT1C receptors. However, propranolol and LY 53857 only antagonised the tachycardiac effects of a high dose of alpha-methyl-5-HT. We hypothesised that the pressor and tachycardiac effects of these agonists may be mediated by 5-HT2 and 5-HT1C receptors, respectively. However, the availability of specific 5-HT1C and/or 5-HT2 receptor antagonists is necessary to verify our hypothesis and before a clear-cut conclusion can be drawn.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
D011985	Receptors, Serotonin	Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.	5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
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
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
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
D006339	Heart Rate	The number of times the HEART VENTRICLES contract per unit of time, usually per minute.	Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
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
D000662	Amphetamines	Analogs or derivatives of AMPHETAMINE. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.
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