Electrophysiological effects of dopamine autoreceptor antagonists, (+)-AJ 76 and (+)-UH 232. 1990

M F Piercey, and J T Lum
CNS Research, Upjohn Company, Kalamazoo, MI 49001.

The weak aminotetralin stimulants, (+)-AJ 76, cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin and (+)-UH 232, cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, were tested for their effects on firing rates of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNPC). (+)-AJ 76 and (+)-UH 232 antagonized the depression of DA neuron firing rates following autoreceptor stimulation by apomorphine. Thus, just as they antagonize DA autoreceptors on presynaptic terminals, these aminotetralins also antagonize the somatodendritic DA autoreceptor. However, in contrast to terminal autoreceptors where (+)-AJ 76 is the most potent antagonist, (+)-UH 232 is the most potent on cell body autoreceptors. (+)-AJ 76 and (+)-UH 232 also reversed the depression of DA neurons arising from activation of negative feedback pathways by amphetamine-induced DA release in postynaptic areas. Based on potencies to reverse amphetamine and apomorphine, respectively, the postsynaptic/presynaptic potency ratios for (+)-AJ 76, (+)-UH 232, and haloperidol were all near unity. It is concluded that (+)-AJ 76 and (+)-UH 232 antagonize both postsynaptic and somatodendritic sites with equal potencies, and that their weak stimulant properties may be due to a preferential antagonism of nerve terminal autoreceptors.

UI MeSH Term Description Entries
D008297 Male Males
D009281 Naphthalenes Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
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
D003712 Dendrites Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS. Dendrite
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005246 Feedback A mechanism of communication within a system in that the input signal generates an output response which returns to influence the continued activity or productivity of that system. Feedbacks
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
D000661 Amphetamine A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE. Desoxynorephedrin,Levoamphetamine,Phenopromin,l-Amphetamine,Amfetamine,Amphetamine Sulfate,Amphetamine Sulfate (2:1),Centramina,Fenamine,Mydrial,Phenamine,Thyramine,levo-Amphetamine,Sulfate, Amphetamine,l Amphetamine,levo Amphetamine

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