Biomaterial Database

Serotonin neurotoxins: recent advances in the mode of administration and molecular mechanism of action. 1981

H G Baumgarten, and S Jenner, and H P Klemm

1. Slow infusion of 5,7-DHT into the left lateral ventricle of nomifensine pretreated, pentobarbitone anaesthetized rats produces moderate, asymmetric regional forebrain 5-HT depletions 24 h after the injection; rapid pulse injection of 5,7-DHT results in more extensive and almost symmetric 5-HT reductions. By the eighth day, both injection procedures cause a comparable pattern of 5-HT depletion throughout the CNS. RAdioactivity distribution patterns (following 14C-5,7-DHT) correlate with the characteristics of 5-HT depletions. The type of anaesthetic used (pentobarbitone; pentobarbitone plus ketamine; ether) has little, if any, influence on the long-term 5-HT reductions in the rat CNS. 2. In forebrain regions, near the ventricle, nomifensine does not totally protect catecholamine fibre systems when pentobarbitone is used as the anaesthetic. However, optimum selectivity is provided by a combination of DMI and nomifensine in animals anaesthetized with a combination of pentobarbitone and ketamine. 3. Reaction of 5,6- and 5,7-DHT with oxygen is essential for these drugs to act as neurotoxins. Both drugs interact with the electron transfer chain of mitochondria (at the site of complex III) resulting in accelerated formation of reactive quinoidal intermediates. Metabolism of 5,7-DHT by MAO contributes to the overall in vivo neurotoxicity of this m-substituted dihydroxytryptamine.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D007839	Functional Laterality	Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot.	Ambidexterity,Behavioral Laterality,Handedness,Laterality of Motor Control,Mirror Writing,Laterality, Behavioral,Laterality, Functional,Mirror Writings,Motor Control Laterality,Writing, Mirror,Writings, Mirror
D008297	Male		Males
D009627	Nomifensine	An isoquinoline derivative that prevents dopamine reuptake into synaptosomes. The maleate was formerly used in the treatment of depression. It was withdrawn worldwide in 1986 due to the risk of acute hemolytic anemia with intravascular hemolysis resulting from its use. In some cases, renal failure also developed. (From Martindale, The Extra Pharmacopoeia, 30th ed, p266)	Hoe-984,Linamiphen,Merital,Nomifensin,Nomifensine Maleate,Nomifensine Maleate (1:1),Hoe 984,Hoe984,Maleate, Nomifensine
D009928	Organ Specificity	Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.	Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
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
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D004102	Dihydroxytryptamines	Tryptamine substituted with two hydroxyl groups in any position. Some are cytotoxic serotonin analogs that are preferentially taken up by serotonergic neurons and then destroy those neurons.
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
D012701	Serotonin	A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.	5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine