GABAA Rγ2 Inhibitors
Chemical inhibitors of the GABAA Rγ2 receptor can interact with the receptor in a variety of ways to inhibit its function. Picrotoxin, for instance, binds to the receptor at a site distinct from the GABA binding site and acts as a non-competitive antagonist. This binding obstructs chloride ion flow through the channel, inhibiting the receptor's typical response to GABA. Similarly, bicuculline competes with GABA for its binding site on the receptor, preventing GABA from activating GABAA Rγ2 and thereby stopping the flow of chloride ions. Tertiapin indirectly affects the receptor by inhibiting GIRK channels that are often co-localized with GABAA Rγ2. The inhibition of these potassium channels can alter the excitability of neurons that also express GABAA Rγ2.
Other inhibitors modulate the receptor through different mechanisms. Zinc sulfate, for example, binds allosterically to the GABAA Rγ2 receptor, distinct from the GABA binding site, and this suppresses the receptor's ability to conduct chloride ions. Penicillin blocks the GABAA receptor channels nonspecifically by binding within the pore of the channel, preventing ion flow. At high concentrations, strychnine can inhibit GABAA receptors, including GABAA Rγ2, by reducing chloride ion conductance. Moreover, gabazine binds competitively to the GABA binding site, blocking GABA from opening the chloride ion channel, and furosemide inhibits the associated chloride channels, thus diminishing the hyperpolarizing effect of GABA activation on GABAA Rγ2. Flumazenil can inhibit the receptor by blocking the modulatory effect of benzodiazepines. Additionally, dihydro-beta-erythroidine at higher concentrations can inhibit the GABAA Rγ2, and secobarbital at high doses can directly gate the chloride channel, leading to receptor desensitization. Lastly, isoflurane at high concentrations can enhance the receptor's desensitization, leading to a decrease in chloride ion flow, thereby inhibiting GABAA Rγ2 function.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Picrotoxin | 124-87-8 | sc-202765 sc-202765A sc-202765B | 1 g 5 g 25 g | $66.00 $280.00 $1300.00 | 11 | |
Picrotoxin acts as a non-competitive antagonist for the GABAA receptor channel. It binds to the receptor at a site distinct from the GABA binding site and inhibits chloride ion flow through the channel, which is the main inhibitory mechanism of GABAA Rγ2. | ||||||
(+)-Bicuculline | 485-49-4 | sc-202498 sc-202498A | 50 mg 250 mg | $80.00 $275.00 | ||
Bicuculline competitively inhibits the GABAA receptor by binding to the GABA binding site, preventing GABA from activating the receptor and thereby inhibiting the chloride ion channel associated with GABAA Rγ2. | ||||||
Zinc | 7440-66-6 | sc-213177 | 100 g | $47.00 | ||
Zinc ions have been shown to inhibit GABAA receptor activity by allosterically modulating the receptor function. It binds to a specific site on the receptor which is different from the GABA binding site, and this binding inhibits the function of GABAA Rγ2 by reducing its ability to conduct chloride ions. | ||||||
Penicillin G sodium salt | 69-57-8 | sc-257971 sc-257971A sc-257971B sc-257971C sc-257971D | 1 mg 10 mg 1 g 5 g 100 g | $25.00 $36.00 $46.00 $168.00 $260.00 | 1 | |
Penicillin is known to nonspecifically block GABAA receptor channels by binding within the pore of the channel, thus inhibiting the function of GABAA Rγ2 by preventing chloride ion flow. | ||||||
Gabazine | 105538-73-6 | sc-211552 | 10 mg | $714.00 | 3 | |
Gabazine is a competitive antagonist of the GABAA receptor. It selectively binds to the GABA binding site on the receptor, inhibiting the function of GABAA Rγ2 by preventing GABA from opening the chloride ion channel. | ||||||
Furosemide | 54-31-9 | sc-203961 | 50 mg | $40.00 | ||
Furosemide is known to inhibit chloride channels associated with GABAA receptors. By binding to the associated Cl- channels, furosemide can inhibit the function of GABAA Rγ2, decreasing the hyperpolarizing effect that GABA typically produces. | ||||||
Flumazenil (Ro 15-1788) | 78755-81-4 | sc-200161 sc-200161A | 25 mg 100 mg | $108.00 $363.00 | 10 | |
Flumazenil is a benzodiazepine antagonist that can inhibit the modulatory effect of benzodiazepines on the GABAA receptor. By blocking this modulatory site, it can inhibit the function of GABAA Rγ2 by preventing the positive allosteric modulation induced by benzodiazepines, thus reducing the receptor's sensitivity to GABA. | ||||||
Isoflurane | 26675-46-7 | sc-470926 sc-470926A | 5 g 25 g | $68.00 $215.00 | 7 | |
Isoflurane is a volatile anesthetic known to modulate several neurotransmitter receptors. At high concentrations, it can inhibit the GABAA receptor function by enhancing the receptor's desensitization, leading to a decrease in chloride ion flow and thereby inhibiting the function of GABAA Rγ2. | ||||||