J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Review

Volume 1, Number 2, June 2009, pages 72-80

5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials

**Table 1a.** Seretonergic receptor subtypes
Receptor Subtype	Second Messenger	Location	Physiological Action	Agonist	Antagonist
8-OH DPAT, 8-Hydroxy-2-(di-n-propylamino) Tetraline; PA, Partial Agonist; LSD, Lysergic Acid Diethylamide; 5-CT, 5 Carboxamidotryptamine; CSF, Cerebrospinal Fluid; 5-HT, 5 Hydroxytryptamine; CTZ, Chemoreceptor Trigger Zone
5-HT_1A	Inhibit adenylate cyclase and activate receptor operated K⁺ channel. Inhibit voltage gated Ca²⁺ channel	CNS: Raphe nuclei, Hippocampus PNS: Cholinergic heteroreceptor in myenteric plexus	1. Seretonergic auto receptor 2. Neuronal inhibition 3. Facilitate Ach and nor adrenaline release 4. Cholinergic nerve terminal in myenteric plexus 5. Hyperphagia (led to obesity)	8-OH-DPAT Buspirone (PA) Ipsapirone Flesinoxan 5-CT Quetiapine	WAY100635 5-F 8-OH DPAT Spiperone Sibutramine
5-HT_1B	Inhibit adenylate cyclase	CNS: subiculum substania nigra PNS: Vascular smooth muscle	1. Seretonergic auto receptor 2. Terminal heteroreceptor to control release of Ach and nor adrenaline 3. Contraction of vascular smooth muscle	5-CT 8-OH-DPAT Sumatriptan Ergotamine (PA)	GR55562 SB224289 SB236057 Methiothepin Cynopindolol
5-HT_1D	Inhibit adenylate cyclase	CNS: cranial blood vessel PNS: Vascular smooth muscle	1. Seretonergic auto receptor 2. GABAergic and Cholinergic heteroreceptor 3. Vasoconstriction of intracranial blood vessel smooth muscle	Sumatriptan Zolmitriptan Nortriptan L694247 Ergotamine (PA)	Methiothepin Ergotamine BRL15572
5-HT_1E	Inhibit adenylate cyclase	CNS: cortex striatum PNS: m-RNA in vascular tissue	Unknown	5-CT (weak agonist) 5-HT	Methiothepin
5-HT_1F	Inhibit adenylate cyclase	CNS: Spinal cord hippocampus PNS: Uterus, mesentery, vascular smooth muscle	Trigeminal (V) neuro inhibition in guinea pig and rat	No selective agonist or antagonist are available

Table 1a. Seretonergic receptor subtypes

Receptor Subtype

Second Messenger

Location

Physiological Action

Agonist

Antagonist

8-OH DPAT, 8-Hydroxy-2-(di-n-propylamino) Tetraline; PA, Partial Agonist; LSD, Lysergic Acid Diethylamide; 5-CT, 5 Carboxamidotryptamine; CSF, Cerebrospinal Fluid; 5-HT, 5 Hydroxytryptamine; CTZ, Chemoreceptor Trigger Zone

5-HT_1A

Inhibit adenylate cyclase and activate receptor operated K⁺ channel. Inhibit voltage gated Ca²⁺ channel

CNS: Raphe nuclei, Hippocampus
PNS: Cholinergic heteroreceptor in myenteric plexus

1. Seretonergic auto receptor
2. Neuronal inhibition
3. Facilitate Ach and nor adrenaline release
4. Cholinergic nerve terminal in myenteric plexus
5. Hyperphagia (led to obesity)

8-OH-DPAT
Buspirone (PA)
Ipsapirone
Flesinoxan
5-CT
Quetiapine

WAY100635
5-F 8-OH DPAT
Spiperone
Sibutramine

5-HT_1B

Inhibit adenylate cyclase

CNS: subiculum substania nigra
PNS: Vascular smooth muscle

1. Seretonergic auto receptor
2. Terminal heteroreceptor to control release of Ach and nor adrenaline
3. Contraction of vascular smooth muscle

5-CT
8-OH-DPAT
Sumatriptan
Ergotamine (PA)

GR55562
SB224289
SB236057
Methiothepin
Cynopindolol

5-HT_1D

Inhibit adenylate cyclase

CNS: cranial blood vessel
PNS: Vascular smooth muscle

1. Seretonergic auto receptor
2. GABAergic and Cholinergic heteroreceptor
3. Vasoconstriction of intracranial blood vessel smooth muscle

Sumatriptan
Zolmitriptan
Nortriptan
L694247
Ergotamine (PA)

Methiothepin
Ergotamine
BRL15572

5-HT_1E

Inhibit adenylate cyclase

CNS: cortex striatum
PNS: m-RNA in vascular tissue

Unknown

5-CT (weak agonist)
5-HT

Methiothepin

5-HT_1F

Inhibit adenylate cyclase

CNS: Spinal cord hippocampus
PNS: Uterus, mesentery, vascular smooth muscle

Trigeminal (V) neuro inhibition in guinea pig and rat

No selective agonist or antagonist are available

**Table 1b.** Seretonergic receptor subtypes
Receptor Subtype	Second Messenger	Location	Physiological Action	Agonist	Antagonist
8-OH DPAT, 8-Hydroxy-2-(di-n-propylamino) Tetraline; PA, Partial Agonist; LSD, Lysergic Acid Diethylamide; 5-CT, 5 Carboxamidotryptamine; CSF, Cerebrospinal Fluid; 5-HT, 5 Hydroxytryptamine; CTZ, Chemoreceptor Trigger Zone
5-HT_2A D receptor	Phospholipase C activation	CNS: cerebral cortex PNS: GI, vascular and bronchial smooth muscle, platelets	1. Neuro excitation 2. Broncho constriction 3. Platelet aggregation 4. Smooth muscle contraction	α-methyl 5-HT 5-CT Sumatriptan 8-OH DPAT LSD	Ketanserin Cyproheptadin Pizotifin Methylsergide Risperidone Olanzapine Clozapine
5-HT_2B	Phospholipase C activation	CNS: cerebellum hypothalamus PNS: Vascular endothelium, stomach	Endothelium dependant vaso relaxation via NO production and stomach fundus contraction	5-CT Sumatriptan BW723C86	RS127445 SB204741
5-HT_2C	Phospholipase C activation	CNS: choroid plexus, hippocampus, hypothala-mus	Modulation of transferin production and modulation of CSF volume	α-methyl 5-HT 5-CT Quipazine	Methylsergide Olanzapine Mesulergine
5-HT₃ M receptor	Ligand gated ion channel	CNS: area postrema PNS: Abdominal visceral afferent neuron	1. Stimulate vomiting by acting on CTZ and by vagal neuro excitation 2. Stimulate nociceptive (pain mediating) nerve ending led to pain	2-me5-HT 5-MeOT	Ondensetron Tropisetron Granisetron
5-HT₄	Activation of adenylate cyclase	CNS: Hippocampus PNS: GIT	Neuronal excitation Increase GI motility	Mosapride Cisapride Zacopride	GR113808 SB204070
5-HT_5A	Unknown	CNS: olfactory bulb, Hebenula	Unknown	No selective agonist or antagonist are available
5-HT_5B	Unknown	CNS: olfactory bulb, Hebenula	Unknown	No selective agonist or antagonist are available

Table 1b. Seretonergic receptor subtypes

Receptor Subtype

Second Messenger

Location

Physiological Action

Agonist

Antagonist

5-HT_2A D receptor

Phospholipase C activation

CNS: cerebral cortex
PNS: GI, vascular and bronchial smooth muscle, platelets

1. Neuro excitation
2. Broncho constriction
3. Platelet aggregation
4. Smooth muscle contraction

α-methyl 5-HT
5-CT
Sumatriptan
8-OH DPAT
LSD

Ketanserin
Cyproheptadin
Pizotifin
Methylsergide
Risperidone
Olanzapine
Clozapine

5-HT_2B

Phospholipase C activation

CNS: cerebellum hypothalamus
PNS: Vascular endothelium, stomach

Endothelium dependant vaso relaxation via NO production and stomach fundus contraction

5-CT
Sumatriptan
BW723C86

RS127445
SB204741

5-HT_2C

Phospholipase C activation

CNS: choroid plexus, hippocampus, hypothala-mus

Modulation of transferin production and modulation of CSF volume

α-methyl 5-HT
5-CT
Quipazine

Methylsergide
Olanzapine
Mesulergine

5-HT₃ M receptor

Ligand gated ion channel

CNS: area postrema
PNS: Abdominal visceral afferent neuron

1. Stimulate vomiting by acting on CTZ and by vagal neuro excitation
2. Stimulate nociceptive (pain mediating) nerve ending led to pain

2-me5-HT
5-MeOT

Ondensetron
Tropisetron
Granisetron

5-HT₄

Activation of adenylate cyclase

CNS: Hippocampus
PNS: GIT

Neuronal excitation
Increase GI motility

Mosapride
Cisapride
Zacopride

GR113808
SB204070

5-HT_5A

Unknown

CNS: olfactory bulb, Hebenula

Unknown

No selective agonist or antagonist are available

5-HT_5B

Unknown

CNS: olfactory bulb, Hebenula

Unknown

No selective agonist or antagonist are available

**Table 1c.** Seretonergic receptor subtypes
Receptor Subtype	Second Messenger	Location	Physiological Action	Agonist	Antagonist
8-OH DPAT, 8-Hydroxy-2-(di-n-propylamino) Tetraline; PA, Partial Agonist; LSD, Lysergic Acid Diethylamide; 5-CT, 5 Carboxamidotryptamine; CSF, Cerebrospinal Fluid; 5-HT, 5 Hydroxytryptamine; CTZ, Chemoreceptor Trigger Zone
5-HT₆	Activation of adenylate cyclase	CNS: caudate putamen, hippocampus PNS: Superior cervical ganglia	Modulation of CNS Ach release	No selective agonist available	SB271046 Methiothepin
5-HT₇	Activation of adenylate cyclase	CNS: hypothalamus PNS: gastrointestinal and vascular smooth muscle	Smooth muscle relaxation	5-HT Sumatriptan 8-OH DPAT	SB258719 Methiothepin

Table 1c. Seretonergic receptor subtypes

Receptor Subtype

Second Messenger

Location

Physiological Action

Agonist

Antagonist

5-HT₆

Activation of adenylate cyclase

CNS: caudate putamen, hippocampus
PNS: Superior cervical ganglia

Modulation of CNS Ach release

No selective agonist available

SB271046
Methiothepin

5-HT₇

Activation of adenylate cyclase

CNS: hypothalamus
PNS: gastrointestinal and vascular smooth muscle

Smooth muscle relaxation

5-HT
Sumatriptan
8-OH DPAT

SB258719
Methiothepin