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Effects of 1-cyclohexyl- and 1-cyclohexyl-N-propargyl-1,2,3,4-tetrahydroisoquinoline on dopaminergic spontaneous discharge in nigral neurons of rats. 2016

Momoko Abe, and Hiroko Munakata, and Kenji Abe, and Toshiaki Saito, and Yoshie Horiguchi, and Hiroshi Nojima, and Kyoji Taguchi
Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, 31-1 Tomitamachi, Koriyama, Fukushima 963-8611, Japan.

1,2,3,4-Tetrahydroisoquinoline (TIQ) and some of its derivatives, such as 1-benzyl-TIQ and 1-methyl-TIQ, are endogenously present in human brain and are thought to contribute to induction or prevention of Parkinson's disease. In the present study, we estimated the effects of the artificially synthesized TIQ derivatives 1-cyclohexyl-TIQ (1-cHex-TIQ) and 1-cyclohexyl-N-propargyl-TIQ (1-cHex-N-proTIQ) on spontaneous nigral dopaminergic discharge in rats. Low to middle doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced a transient and significant, but not relatively potent, increase in the firing rate, followed by a sustained decrease with higher doses. 1-cHex-TIQ increased the firing frequency at low and high doses. In contrast, 1-cHex-N-proTIQ had no effects on spontaneous firing. Although intraperitoneal pretreatment with 1-cHex-TIQ did not inhibit this MPTP-induced decrease in firing, pretreatment with 1-cHex-N-proTIQ significantly depressed this decreased firing in a dose-dependent and long-lasting manner. Selegiline, a monoamine oxidase type B inhibitor that is used as a therapeutic drug for Parkinson's disease, also significantly inhibited the decrease in dopaminergic spontaneous firing induced by MPTP, but the effect was transient. These results suggest that although the decrease in firing induced by 1-cHex-TIQ is clearly more potent compared to that induced by MPTP, its effect is eliminated by adding an N-propargyl functional group. The antagonizing effect of 1-cHex-N-proTIQ on MPTP-induced firing loss may be exerted by a different mechanism than that of selegiline.

UI MeSH Term Description Entries
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
D009498 Neurotoxins Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. Alpha-Neurotoxin,Excitatory Neurotoxin,Excitotoxins,Myotoxin,Myotoxins,Neurotoxin,Alpha-Neurotoxins,Excitatory Neurotoxins,Excitotoxin,Alpha Neurotoxin,Alpha Neurotoxins,Neurotoxin, Excitatory,Neurotoxins, Excitatory
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
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
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
D013378 Substantia Nigra The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis. Nigra, Substantia,Nigras, Substantia,Substantia Nigras
D015259 Dopamine Agents Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons. Dopamine Drugs,Dopamine Effect,Dopamine Effects,Dopaminergic Agents,Dopaminergic Drugs,Dopaminergic Effect,Dopaminergic Effects,Agents, Dopamine,Agents, Dopaminergic,Drugs, Dopamine,Drugs, Dopaminergic,Effect, Dopamine,Effect, Dopaminergic,Effects, Dopamine,Effects, Dopaminergic
D015632 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease. MPTP,N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

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