SNX-482 is a toxin from the tarantula Hysterocrates gigas

Hysterocrates gigas

Hysterocrates gigas or the Giant baboon spider, is a member of the tarantula family, Theraphosidae. It is also known as the Cameroon red baboon spider.-Description:...

. It acts as a high-affinity blocker

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

 of R-type

R-type calcium channel

The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms the pore through which calcium enters the cell and determines most of the channel's properties...

 Ca2+ (Cav2.3) channels, but at higher concentrations it can also block other Ca2+ channels and Na+ channels.

Homology

SNX-482 is homologous to the spider peptides grammatoxin

Grammotoxin

Grammotoxin is a toxin in the venom of the tarantula Grammostola spatulata. It is a protein toxin that inhibits P-, Q- and N-type voltage-gated calcium channels in neurons...

 S1A and hanatoxin.

Target

Cav2.3 (alpha1E, R-type) channel (strong affinity), L-type Ca2+ channel, P/Q type Ca2+ channel, Na+ channel .

Mode of action

The compound was initially identified as a selective, voltage-dependent inhibitor of Cav2.3 (a1E, R-type) channels. SNX-482 inhibits native R-type Ca2+ currents at weak nanomolar concentrations in rat neurohypophyseal nerve terminals. However, it does not influence R-type Ca2+ currents at concentrations of 200-500 nM in several types of rat central neurons. Washout could only moderately reverse the R-type Ca2+ channel inhibition after treatment with 200 nM SNX-482. However, application of strong voltage reverses the blocking of R-type Ca2+ channels. SNX-482 needs to interact with a1E domains III and IV to play a role in the significant inhibition of R-type channel gating. Although SNX-482 is generally viewed as a selective inhibitor of Cav2.3 (a1E, R-type) channels, more recently it was shown that it can also inhibit L-type or P/Q type Ca2+ channels and incompletely block Na+ channels.

Research and therapeutic use

SNX-482 has been used to elucidate the roles of theaflavin-3-G

Theaflavin-3-gallate

Theaflavin-3-gallate is a theaflavin derivative. It can be found in black tea....

 in transmitter

Neurotransmitter

Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 release; furthermore, some research indicated that it inhibits neuronal responses in a neuropathic pain

Neuropathic pain

Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...

 model, so it is possible that SNX-482 can be used to reduce dorsal horn neuronal pain in neuropathic pain

Neuropathic pain

Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...

 therapy

Therapy

This is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...

.