Biomaterial Database

Inhibition of dorsal raphe cell firing by MDL 73005EF, a novel 5-HT1A receptor ligand. 1991

J S Sprouse

Marion Merrell Dow Research Institute, Cincinnati, OH 45215.

The effect of a novel ligand for the 5-HT1A receptor subtype, MDL 73005EF, on the firing rate of serotonergic dorsal raphe neurons was assessed in rat midbrain slices maintained in vitro. Superfusion with MDL 73005EF inhibited neuronal firing in a concentration-dependent manner. Based upon IC50 values, MDL 73005EF was equipotent with buspirone (129 +/- 34 vs. 97 +/- 8 nM, respectively) but significantly less potent than 8-OH-DPAT (8-hydroxy-2(di-n-propylamino)tetralin; 7 +/- 2 nM). Pretreatment with (-)-propranolol (1 microM), a mixed 5-HT1A/B receptor antagonist, blocked by 50% the inhibition of unit activity elicited by MDL 73005EF. Taken together, these data suggest that MDL 73005EF is an agonist at the somatodendritic autoreceptor on dorsal raphe neurons, a 5-HT1A receptor which regulates in part the pacemaker activity of these cells. The results are discussed in the context of receptor reserve, recently proposed to explain apparent discrepancies in the actions of agonists at pre- and postsynaptic 5-HT1A sites.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D008297	Male		Males
D008636	Mesencephalon	The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the PONS and the DIENCEPHALON. Midbrain contains two major parts, the dorsal TECTUM MESENCEPHALI and the ventral TEGMENTUM MESENCEPHALI, housing components of auditory, visual, and other sensorimoter systems.	Midbrain,Mesencephalons,Midbrains
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011433	Propranolol	A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.	Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D011903	Raphe Nuclei	Collections of small neurons centrally scattered among many fibers from the level of the TROCHLEAR NUCLEUS in the midbrain to the hypoglossal area in the MEDULLA OBLONGATA.	Caudal Linear Nucleus of the Raphe,Interfascicular Nucleus,Nucleus Incertus,Rostral Linear Nucleus of Raphe,Rostral Linear Nucleus of the Raphe,Superior Central Nucleus,Central Nucleus, Superior,Incertus, Nucleus,Nuclei, Raphe,Nucleus, Interfascicular,Nucleus, Raphe,Nucleus, Superior Central,Raphe Nucleus
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
D002065	Buspirone	An anxiolytic agent and serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the BENZODIAZAPINES, but it has an efficacy comparable to DIAZEPAM.	Anxut,Apo-Buspirone,Bespar,Busp,Buspar,Buspirone Hydrochloride,Gen-Buspirone,Lin-Buspirone,MJ-9022-1,N-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-1-cyclopentanediacetamide,Neurosine,Novo-Buspirone,Nu-Buspirone,PMS-Buspirone,Ratio-Buspirone,Apo Buspirone,Gen Buspirone,Hydrochloride, Buspirone,Lin Buspirone,MJ 9022 1,MJ90221,Novo Buspirone,Nu Buspirone,PMS Buspirone,Ratio Buspirone
D003712	Dendrites	Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.	Dendrite
D004147	Dioxins	A family of compounds that contain the 1,4-dioxin structure. Many specific dioxin derivatives are listed as CARCINOGENS; TERATOGENS; or MUTAGENS.	Dioxin