Endothelin antagonists

[Neuroprotection]

Prescribed endothelin antagonists it would be interesting to hear your experiences particularly if you have combined them with opioids Endothelin antagonists are drugs used to control high blood pressure and they work by blocking the effect of the peptide endothelin at various receptor sites. Apart from being located in blood vessels endothelin receptors are expressed in high concentration in neurons throughout the brain, showing that endothelin peptide likely has a role as some sort of neurotransmitter or Neuromodulator. Such neurotransmission is very likely to be excitatory as injection of Endothelin directly into the brain of rats induced severe neurotoxicity and seizures often resulting in death, or severe memory impairment in survivors. Endothelin antagonists have been shown to be Neuroprotective under many circumstances including physical brain injury or exposure to exogenous and endogenous neurotoxins.
Another fascinating fact I have Red is that endothelin antagonists strongly reverse opioid tolerance without acting on the opioid receptor, rather they work by re joining G proteins which have been on coupled from the opioid receptor during tolerance development.
In animal tests endothelin antagonists reduced tolerance in animals fully dependent on morphine back to control levels. I really hope this applies to humans too.
Endothelin antagonists are also thought to have anxiety reducing and antidepressant effects as well as a possible antipsychotic effect that does not rely on dopaminergic signalling blockade.
Have any of you been Prescribed endothelin antagonists it would be interesting to hear your experiences particularly if you have combined them with

 

[Pilll_head]

Interesting. I do research at one of the major drug companies. If endothelin antagonists resensitize the opioid GPCR then I would imagine they might have to be contraindicated with opioid painkillers just because of the increased possibility of overdose. But the tolerance reversal idea sounds intriguing, wonder if there's any Kratom or sub users here who feel that they aren't seeing enough benefit from it and want something better?

 

[Neuroprotection]

Interesting. I do research at one of the major drug companies. If endothelin antagonists resensitize the opioid GPCR then I would imagine they might have to be contraindicated with opioid painkillers just because of the increased possibility of overdose. But the tolerance reversal idea sounds intriguing, wonder if there's any Kratom or sub users here who feel that they aren't seeing enough benefit from it and want something better?

As a researcher do you have access to any endothelin antagonists and if so could you conduct an experiment to see if they really reverse opioid tolerance or at least enhance their effects

 

[Neuroprotection]

Anyone else tried endothelin antagonists, I would like to but unfortunately I do not have access to them. Maybe they are not as common as other anti-hypertensive drugs such as beta blockers and calcium channel blockers. I'd really appreciate it if anyone could post their experiences with endothelin antagonists.

 

[Cotcha Yankinov]

Hey neuro I thought I would add in here another miscellaneous tolerance opoid tolerance prevention route I came across, cholecystokinin antagonism https://en.m.wikipedia.org/wiki/Cholecystokinin_antagonist

Apparently mediated by the cholecystokinin B receptors. No idea how it works though.

 

[Pilll_head]

As a researcher do you have access to any endothelin antagonists and if so could you conduct an experiment to see if they really reverse opioid tolerance or at least enhance their effects

Not really, I just do chemistry. The biological experiments are conducted by a different division in most of the big pharma research hubs. Some scientists come up with ideas such as the one you described, they can submit a proposal to the senior management and get it funded to try it out on small scale. But you have to have connections if you want to stand a chance.