A channel modulator , or ion channel modulator , is a type of drug which modulates ion channels . They include channel blockers and channel openers .[1]
Direct modulators [ ]
Ion channels are typically categorised by gating mechanism and by the ion they conduct. Note that an ion channel may overlap between different categories. Some channels conduct multiple ion currents and some are gated by multiple mechanisms.
Examples of targets for modulators include:
Voltage gated ion channels
Ligand gated ion channels
Ion channels gated by other mechanisms (e.g. light gated and mechanosensitive ion channels ). These types of channels can also be pharmacologically modulated. For lists of the substances that pharmacologically modulate them, see their respective articles.
Indirect modulators [ ]
Ion channels can also be modulated indirectly. For example with G protein coupled receptors (GPCRs), for G protein coupled inward rectifier potassium channels (GIRKs) and M channels. Ion channels can also be modulated by reuptake inhibitors and releasing agents .
See also [ ]
References [ ]
^ Birch, PJ; Dekker, LV; James, IF; Southan, A; Cronk, D (1 May 2004). "Strategies to identify ion channel modulators: current and novel approaches to target neuropathic pain". Drug Discovery Today . 9 (9): 410–8. doi :10.1016/S1359-6446(04)03043-0 . PMID 15081958 .
Pharmacomodulation
Types
♦ Receptor : Agonist
Partial agonist
Antagonist
Inverse agonist
Positive allosteric modulator (PAM)
Negative allosteric modulator (NAM)
♦ Miscellaneous: Precursor
Cofactor
Classes
Enzyme see Enzyme inhibition
Ion channel See Ion channel modulators
Receptor &transporter
Miscellaneous
Cofactor (see Enzyme cofactors )
Precursor (see Amino acids )
Calcium
Potassium
VGKCs
Blockers
hERG (KCNH2, Kv 11.1)-specific: Ajmaline
Amiodarone
AmmTX3
Astemizole
Azaspiracid
AZD1305
Azimilide
Bedaquiline
BeKm-1
BmTx3
BRL-32872
Chlorpromazine
Cisapride
Clarithromycin
Darifenacin
Dextropropoxyphene
Diallyl trisulfide
Domperidone
E-4031
Ergtoxins
Erythromycin
Gigactonine
Haloperidol
Ketoconazole
Norpropoxyphene
Orphenadrine
Pimozide
PNU-282,987
Promethazine
Quinidine
Ranolazine
Roxithromycin
Sertindole
Solifenacin
Tamulotoxin
Terodiline
Terfenadine
Thioridazine
Tolterodine
Vanoxerine
Vernakalant
Activators
KCNQ (Kv 7) -specific: Flupirtine
Retigabine
IRKs
Blockers
GIRK -specific: Barium
Caramiphen
Cloperastine
Clozapine
Dextromethorphan
Ethosuximide
Ifenprodil
Tertiapin
Tipepidine
Activators
KATP -specific:
Bimakalim
Cromakalim
Diazoxide
Levcromakalim
Minoxidil
Nicorandil
Pinacidil
KCa
Blockers
BKCa -specific: Ethanol (alcohol)
GAL-021
Activators
K2Ps
Blockers
12-O-Tetradecanoylphorbol-13-acetate
Arachidonic acid
Fluoxetine
Norfluoxetine
Activators
Sodium
VGSCs
Blockers
Toxins: Conotoxins
Neosaxitoxin
Saxitoxin
Tetrodotoxin
Zetekitoxin AB
Others: Buprenorphine
Evenamide
Menthol (mint )
Safinamide
Tricyclic antidepressants
Activators
ENaC
Blockers
Amiloride
Benzamil
Triamterene
Activators
ASICs
Blockers
Amiloride
Aspirin
Ibuprofen
Chloride
Others
See also: Receptor/signaling modulators • Transient receptor potential channel modulators
TRPA
Activators
4-Hydroxynonenal
4-Oxo-2-nonenal
4,5-EET
12S-HpETE
15-Deoxy-Δ12,14 -prostaglandin J2
α-Sanshool (ginger , Sichuan and melegueta peppers )
Acrolein
Allicin (garlic )
Allyl isothiocyanate (mustard , radish , horseradish , wasabi )
AM404
ASP-7663
Bradykinin
Cannabichromene (cannabis )
Cannabidiol (cannabis )
Cannabigerol (cannabis )
Cinnamaldehyde (cinnamon )
CR gas (dibenzoxazepine; DBO)
CS gas (2-chlorobenzal malononitrile)
Cuminaldehyde (cumin )
Curcumin (turmeric )
(celery )
Diallyl disulfide
Dicentrine (Lindera spp.)
Formalin
Gingerols (ginger )
Hepoxilin A3
Hepoxilin B3
Hydrogen peroxide
Icilin
Isothiocyanate
JT-010
(celery , Angelica acutiloba )
Linalool (Sichuan pepper , thyme )
Methylglyoxal
Methyl salicylate (wintergreen )
N-Methylmaleimide
Nicotine (tobacco )
Oleocanthal (olive oil )
Paclitaxel (Pacific yew )
Paracetamol (acetaminophen)
PF-4840154
Phenacyl chloride
Polygodial (Dorrigo pepper )
Shogaols (ginger , Sichuan and melegueta peppers )
Tear gases
Tetrahydrocannabinol (cannabis )
Tetrahydrocannabiorcol
Thiopropanal S-oxide (onion )
Umbellulone (Umbellularia californica )
WIN 55,212-2
Blockers
TRPC
TRPM
Activators
ADP-ribose
Calcium (intracellular)
CIM-0216
Cold
Cooling Agent 10
Eucalyptol (eucalyptus )
Geraniol
Hydroxycitronellal
Icilin
Linalool
Menthol (mint )
Pregnenolone sulfate
(Ruta graveolens )
Steviol glycosides (e.g., stevioside ) (Stevia rebaudiana )
Sweet tastants (e.g., glucose , fructose , sucrose ; indirectly)
WS-12
Blockers
TRPML
TRPP
Activators
Triptolide (Tripterygium wilfordii )
Blockers
TRPV
Activators
2-APB
5',6'-EET
9-HODE
9-oxoODE
12S-HETE
12S-HpETE
13-HODE
13-oxoODE
20-HETE
α-Sanshool (ginger , Sichuan and melegueta peppers )
Allicin (garlic )
AM404
Anandamide
(Andrographis paniculata )
Camphor (camphor laurel , rosemary , camphorweed , African blue basil , camphor basil )
Cannabidiol (cannabis )
Cannabidivarin (cannabis )
Capsaicin (chili pepper )
Carvacrol (oregano , thyme , pepperwort , wild bergamot , others)
DHEA
Diacyl glycerol
Dihydrocapsaicin (chili pepper )
Estradiol
Eugenol (basil , clove )
Evodiamine (Euodia ruticarpa )
Gingerols (ginger )
GSK1016790A
Heat
Hepoxilin A3
Hepoxilin B3
Homocapsaicin (chili pepper )
Homodihydrocapsaicin (chili pepper )
Incensole (incense )
Lysophosphatidic acid
Low pH (acidic conditions)
Menthol (mint )
N-Arachidonoyl dopamine
N-Oleoylethanolamide
Nonivamide (PAVA) (PAVA spray )
Nordihydrocapsaicin (chili pepper )
Paclitaxel (Pacific yew )
Paracetamol (acetaminophen)
Phenylacetylrinvanil
Phorbol esters (e.g., )
Piperine (black pepper , long pepper )
Polygodial (Dorrigo pepper )
Probenecid
Protons
RhTx
(Ruta graveolens )
Resiniferatoxin (RTX) (Euphorbia resinifera /pooissonii )
Shogaols (ginger , Sichuan and melegueta peppers )
Tetrahydrocannabivarin (cannabis )
Thymol (thyme , oregano )
Tinyatoxin (Euphorbia resinifera /pooissonii )
Tramadol
Vanillin (vanilla )
Zucapsaicin
Blockers
See also: Receptor/signaling modulators • Ion channel modulators