Methylphenidate-like effects of the new antidepressant drug nomifensine (HOE 984). 1976

C Braestrup, and J Scheel-Krüger

Nomifensine (HOE 984) belongs to a chemically new class of drugs with reported antidepressant properties. Nomifensine, like methylphemidate, d-amphetamine and apomorphine, induces strong, intense stereotypes behaviour in the rat. The nomifensine-induced stereotyped behaviour was completely antagonized by pretreatment with reserpine (7.5 mg/kg, 18 h) but not by short-time pretreatment with alpha-methyltyrosine (250 mg/kg, 2 h.) Nomifensine thus differs from d-amphetamine and apomorphine but resembles methylphenidate on stereotyped behaviour. Nominfensine, M1 (8-amino-2-methyl-4-(4-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline fumarate) (Hoechst), methylphenidate and d-amphetamine induced a strong increase in the brain level of homovanillec acid (HVA), whereas the dopamine uptake inhibitor benztropine induced no changes in HVA and cocaine induced only a small increase. Nomifensine and the M1 metabolite, like methylphenidate, also increased 3,4-dihydroxyphenylacetic acid (DOPAC) whereas amphetamine, apomorphine, benztropine and cocaine decreased this dopamine metabolite. This suggests that the stereotyped licking and/or biting activities in the rat are related to dopamine releasing properties of nomifensine, methylphenidate and amphetamine. This is further supported by an inverse relationship between the in vitro dopamine uptake inhibitory concentrations and the sterotypy-inducing dose levels of nomifensine and d-amphetamine. Amphetamine caused a strong, and nomifensine and apormorphine a week increase in brain 3-methoxy-4-hydroxyphenylglycol (MOPEG).

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008297 Male Males
D008774 Methylphenidate A central nervous system stimulant used most commonly in the treatment of ATTENTION DEFICIT DISORDER in children and for NARCOLEPSY. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE. The d-isomer of this drug is referred to as DEXMETHYLPHENIDATE HYDROCHLORIDE. Centedrin,Concerta,Daytrana,Equasym,Metadate,Methylin,Methylphenidate Hydrochloride,Phenidylate,Ritalin,Ritalin-SR,Ritaline,Tsentedrin,Hydrochloride, Methylphenidate,Ritalin SR
D012110 Reserpine An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. Raunervil,Raupasil,Rausedil,Rausedyl,Serpasil,Serpivite,V-Serp,V Serp
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D003913 Dextroamphetamine The d-form of AMPHETAMINE. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. d-Amphetamine,Curban,Dexamfetamine,Dexamphetamine,Dexedrine,Dextro-Amphetamine Sulfate,DextroStat,Dextroamphetamine Sulfate,Oxydess,d-Amphetamine Sulfate,dextro-Amphetamine,Dextro Amphetamine Sulfate,Sulfate, Dextroamphetamine,d Amphetamine,d Amphetamine Sulfate,dextro Amphetamine
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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

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