Biomaterial Database

The effects of mirtazapine on central noradrenergic and serotonergic neurotransmission. 1995

T de Boer

Department of Neuropharmacology, Scientific Development Group, N.V. Organon, The Netherlands.

Mirtazapine is a new antidepressant with a unique mode of action: it preferentially blocks the noradrenergic alpha2-auto- and heteroreceptors held responsible for controlling noradrenaline and serotonin release. In addition, mirtazapine has a low affinity for serotonin (5-HT)1A receptors but potently blocks 5-HT2 and 5-HT3 receptors. It increases serotonergic cell-firing in the dorsal raphe and 5-HT release in the hippocampus as measured by microdialysis. These effects are explained by noradrenergic enhancement of 5-HT cell-firing and blockade of noradrenaline-mediated inhibition of hippocampal 5-HT release. Because mirtazapine blocks 5-HT2 and 5-HT3 receptors, only 5-HT1-mediated transmission is enhanced. The noradrenergic activation and the consequent indirect enhancement of serotonergic transmission most probably underlie the marked therapeutic activity of mirtazapine. The blockade of 5-HT2 and 5-HT3 receptors prevents development of the side effects associated with non-selective 5-HT activation and may contribute to the anxiolytic and sleep-improving properties of this new compound. Therefore mirtazapine can be described as a noradrenergic and specific serotonergic antidepressant (NaSSA).

UI	MeSH Term	Description	Entries
D008803	Mianserin	A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors.	Lerivon,Mianserin Hydrochloride,Mianserin Monohydrochloride,Org GB 94,Tolvon,Hydrochloride, Mianserin,Monohydrochloride, Mianserin
D011941	Receptors, Adrenergic	Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction.	Adrenergic Receptors,Adrenoceptor,Adrenoceptors,Norepinephrine Receptor,Receptors, Epinephrine,Receptors, Norepinephrine,Adrenergic Receptor,Epinephrine Receptors,Norepinephrine Receptors,Receptor, Adrenergic,Receptor, Norepinephrine
D011985	Receptors, Serotonin	Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.	5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
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
D003866	Depressive Disorder	An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.	Depression, Endogenous,Depression, Neurotic,Depression, Unipolar,Depressive Syndrome,Melancholia,Neurosis, Depressive,Unipolar Depression,Depressions, Endogenous,Depressions, Neurotic,Depressions, Unipolar,Depressive Disorders,Depressive Neuroses,Depressive Neurosis,Depressive Syndromes,Disorder, Depressive,Disorders, Depressive,Endogenous Depression,Endogenous Depressions,Melancholias,Neuroses, Depressive,Neurotic Depression,Neurotic Depressions,Syndrome, Depressive,Syndromes, Depressive,Unipolar Depressions
D006634	Histamine H1 Antagonists	Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.	Antihistamines, Classical,Antihistaminics, Classical,Antihistaminics, H1,Histamine H1 Antagonist,Histamine H1 Receptor Antagonist,Histamine H1 Receptor Antagonists,Histamine H1 Receptor Blockaders,Antagonists, Histamine H1,Antagonists, Histamine H1 Receptor,Antihistamines, Sedating,Blockaders, Histamine H1 Receptor,First Generation H1 Antagonists,H1 Receptor Blockaders,Histamine H1 Blockers,Receptor Blockaders, H1,Antagonist, Histamine H1,Classical Antihistamines,Classical Antihistaminics,H1 Antagonist, Histamine,H1 Antagonists, Histamine,H1 Antihistaminics,Sedating Antihistamines
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000078785	Mirtazapine	A piperazinoazepine tetracyclic compound that enhances the release of NOREPINEPHRINE and SEROTONIN through blockage of presynaptic ALPHA-2 ADRENERGIC RECEPTORS. It also blocks both 5-HT2 and 5-HT3 serotonin receptors and is a potent HISTAMINE H1 RECEPTOR antagonist. It is used for the treatment of depression, and may also be useful for the treatment of anxiety disorders.	(N-Methyl-11C)mirtazapine,(S)-Mirtazapine,6-Azamianserin,Esmirtazapine,Norset,ORG 3770,ORG-3770,Org 50081,Remergil,Remeron,Rexer,Zispin,6 Azamianserin,ORG3770
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
D000929	Antidepressive Agents, Tricyclic	Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However, the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system.	Antidepressants, Tricyclic,Tricyclic Antidepressant,Tricyclic Antidepressant Drug,Tricyclic Antidepressive Agent,Tricyclic Antidepressive Agents,Antidepressant Drugs, Tricyclic,Agent, Tricyclic Antidepressive,Agents, Tricyclic Antidepressive,Antidepressant Drug, Tricyclic,Antidepressant, Tricyclic,Antidepressive Agent, Tricyclic,Drug, Tricyclic Antidepressant,Drugs, Tricyclic Antidepressant,Tricyclic Antidepressant Drugs,Tricyclic Antidepressants