Electrophysiological evaluation of a partial agonist of dopamine receptors. 1987

M F Piercey, and W E Hoffmann, and G D Vogelsang, and M Travis
CNS Research, Upjohn Company, Kalamazoo, Michigan.

The ergot derivative trans-dihydrolisuride (TDHL) was tested for its effects on firing rates of dopaminergic (DA) neurons located in the substantia nigra pars compacta of chloral hydrate-anesthetized rats. Using extracellular single-barreled microelectrodes, DA neurons were identified by their long duration, positive-negative action potentials and their slow bursting pattern of spontaneous firing, as well as by the location of recording sites through histological recoveries of dye deposits. Like haloperidol and clozapine, which are full DA receptor antagonists, TDHL antagonized the depression in DA neuron firing induced by systemic amphetamine. However, where full antagonists completely reversed the amphetamine effect, TDHL could do so only partially, the maximal effect being around half. Like DA agonists, but unlike DA antagonists, TDHL also depressed the spontaneous firing rates of DA neurons. But whereas the full agonist apomorphine completely inhibited firing of DA neurons, TDHL only depressed firing rates by about half, even at high doses. These data support the contention that TDHL is a partial DA agonist.

UI MeSH Term Description Entries
D008090 Lisuride An ergot derivative that acts as an agonist at dopamine D2 receptors (DOPAMINE AGONISTS). It may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors (SEROTONIN RECEPTOR AGONISTS). Lysuride Hydrogen Maleate,Methylergol Carbamide,Arolac,Cuvalit,Dopergin,Dopergine,Lisuride Hydrochloride,Lisuride Maleate,Lisuride Maleate (1:1),Lisuride Maleate, (8beta)-Isomer,Lisuride Mesylate,Lisuride Phosphate (1:1),Lisuride, (8alpha)-(+-)-Isomer,Lysenyl,Lysurid,Revanil,Carbamide, Methylergol,Hydrochloride, Lisuride,Hydrogen Maleate, Lysuride,Maleate, Lisuride,Mesylate, Lisuride
D008297 Male Males
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
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
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
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
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
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D004873 Ergolines A series of structurally-related alkaloids that contain the ergoline backbone structure. Ergoline
D006220 Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) Haldol

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