5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a

5-HT receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the Central nervous system, central and peripheral nervous systems ...

, but also denotes the human

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

encoding it. 5-HT_1D acts on the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

, and affects locomotion and

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

. It also induces

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

in the brain.

Tissue distribution

5HT_1D receptors are found at low levels in the basal ganglia (globus pallidus, substantia nigra, caudate putamen), the hippocampus, and in the cortex.

Structure

5HT_1D receptor is a

G protein G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), ...

linked receptor that activates an

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

messenger cascade to produce an inhibitory response by decreasing cellular levels of cAMP. The 5HT_1D is a 7-TM receptor. A large intercellular loop between TM-5 and TM-6 is believed to be associated with coupling to a second messenger. Agonists might bind in a manner that utilizes an

aspartate Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protein ...

residue in TM-3 and residues in the TM-4, TM-5 and TM-6. A human clone containing an intronless

open reading frame In molecular biology, reading frames are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible reading frames ...

was found to encode 377 amino acids of the 5HT_1D receptor. The gene has been localized on chromosome 1, region 1p34.3-36.3

Ligands

Agonists

Molecular modelling Molecular modelling encompasses all methods, theoretical and computational, used to model or mimic the behaviour of molecules. The methods are used in the fields of computational chemistry, drug design, computational biology and materials scien ...

has provided a picture of the agonistic binding site of 5HT_1D. The

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

residues within the receptor binding site region have been identified. This is a valuable guide to design potential 5HT_1D receptor agonists. When

sumatriptan Sumatriptan, sold under the brand name Imitrex among others, is a medication used to treat migraine headaches and cluster headaches. It is taken Oral administration, orally, Nasal administration, intranasally, or by Subcutaneous injection, su ...

binds there is major conformational change in both ligand and receptor in the binding pocket. *

5-(Nonyloxy)tryptamine 5-(Nonyloxy)tryptamine (5-NOT) is a tryptamine derivative which acts as a selective agonist at the 5-HT1B receptor. Increasing the O-alkoxy chain length in this series gives generally increasing potency and selectivity for 5-HT1B, with highest a ...

Sumatriptan Sumatriptan, sold under the brand name Imitrex among others, is a medication used to treat migraine headaches and cluster headaches. It is taken Oral administration, orally, Nasal administration, intranasally, or by Subcutaneous injection, su ...

(

vasoconstrictor Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

migraine Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

) *

Ergotamine Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitter ...

(

) *

Zolmitriptan Zolmitriptan, sold under the brand name Zomig among others, is a serotonergic drug, serotonergic medication which is used in the acute treatment of migraine attacks with or without aura (symptom), aura and cluster headaches. It is taken oral adm ...

5-Carboxamidotryptamine 5-Carboxamidotryptamine (5-CT) is a tryptamine derivative closely related to the neurotransmitter serotonin. 5-CT acts as a non-selective, high-affinity full agonist at the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT5A, and 5-HT7 receptors, as well as ...

(5-CT) * 5-(t-Butyl)-N-methyltryptamine *

CP-135807 CP-135807 is a drug which acts as a potent and selective agonist for the 5-HT1D serotonin receptor, and is used to study the function of this receptor subtype. See also * 4-HO-MPMI * 5-MeO-MPMI * Eletriptan Eletriptan, sold under the bra ...

* CP-286601 * PNU-109291 ((S)-3,4-Dihydro-1- -[4-(4-methoxyphenyl)-1-piperazinylthyl">-(4-methoxyphenyl)-1-piperazinyl.html" ;"title="-[4-(4-methoxyphenyl)-1-piperazinyl">-[4-(4-methoxyphenyl)-1-piperazinylthylN-methyl-1H-2-benzopyran-6-carboxamide) * PNU-142633 ((1S)-1-[2-[4-[4-(Aminocarbonyl)phenyl]-1-piperazinyl]ethyl]-3,4-dihydro-N-methyl-1H-2-benzopyran-6-carboxamide) * GR-46611 (3-[3-(2-Dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide) * L-694247 (2-[5-[3-(4-Methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine) *

L-760790 L-760,790 is an experimental drug from the substituted tryptamine family, which acts as a selective agonist for the 5-HT1D serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-cou ...

* L-772405

Antagonists

Ziprasidone Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The intramuscular form may be used for ...

(

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neurol ...

Methiothepin Metitepine (; developmental code names Ro 8-6837 (maleate), VUFB-6276 (mesylate)), also known as methiothepin, is a drug described as a " psychotropic agent" of the tricyclic or tetracyclic group which was never marketed. It acts as a non-sele ...

(

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

) *

Yohimbine Yohimbine, also known as quebrachine, is an indole alkaloid derived from the bark of the African tree '' Pausinystalia johimbe'' (yohimbe); also from the bark of the unrelated South American tree '' Aspidosperma quebracho-blanco''. Yohimbine is ...

(

aphrodisiac An aphrodisiac is a substance that increases libido, sexual desire, sexual attraction, sexual pleasure, or sexual behavior. These substances range from a variety of plants, spices, and foods to synthetic chemicals. Natural aphrodisiacs, such as ...

) *

Metergoline Metergoline (, ), also known as methergoline and sold under the brand names Contralac (veterinary) and Liserdol (clinical), is a monoaminergic medication of the ergoline group which is used as a prolactin inhibitor in the treatment of hyperprola ...

BRL-15572 BRL-15,572 is a drug which acts as a selective antagonist for the serotonin receptor subtype 5-HT1D, with around 60x selectivity over other related receptors. The 5-HT1D receptor has a very similar pharmacology to the closely related 5-HT1B rec ...

* Vortioxetine (

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

) * GR-127935 (mixed 5-HT_1B/1D antagonist) * LY-310762 * LY-367642 * LY-456219 * LY-456220

References

External links

* *