The role of HEPES in pain control and reversal of demyelinating injury

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) is a hydrogen ion buffer which has a good buffering capacity in the pH range of 6.8~8.2 and can control a constant pH for a long time. Recently, HEPES can also as a composition of pain control agents, and reversing demyelinating damage.


The researchers described the use of HEPES and its derivatives as an analgesic, and anti-tumor agent for stabilizing cells, especially neuronal membranes, and reversing demyelinating damage. The HEPES composition is also used to treat withdrawal symptoms after treatment with antidepressants and selective serotonin inhibitors (SSRI); HEPES is also used as an analgesic for the treatment of pain associated with one or more cancers, and side effects after chemotherapy, including cognitive impairment.


The mechanism of action of HEPES includes:
(i) analgesic activity, possibly associated with prolonged anti-anandamide action, with no significant side effects compared to opioids;
(ii) anti-tumor activity may be related to previously discovered mechanisms using promethazine;
(iii) it is possible to stabilize cells, especially neuronal membranes, by modulating various ion channels;
(iv) Reversing demyelinating damage.
In an embodiment, HEPES and its derivatives are dissolved in sterile water, buffer, saline or other pharmaceutically acceptable carrier: (1) HEPES is dissolved in sterile water for oral, subcutaneous, parenteral, intravenous, intraperitoneal or intramuscular injection with administration of 10-100 mg/kg on a body weight basis once a day; (2) in combination with other carriers, such as an antidepressant selected from the group consisting of benzodiazepines, SSRI, serotonin-norepinephrine intake inhibitors (SNRI), noradrenergic and specific serotoninergic antidepressants (NaSSAs), norepinephrine (norepinephrine) reuptake inhibitors (NRI), norepinephrine-dopamine Reuptake inhibitors (NDRI), selective serotonin reuptake enhancers (SSRE), melatonin agonists, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOI) and SSRI including citalopram tapropren, fluoxetine, fluvoxamine, paroxetine, sertraline, mermilidine or any combination thereof.

The product is administered on a weight basis and the minimum effective daily dose determined is 70~75 mg/kg. The material can be administered safely by oral or parenteral route. The inventors have observed in many cases that the drug can be administered by two routes without any significant side effects.


HEPES is a zwitterionic molecule that is commonly used as a buffer in animal and human cell cultures. Studies have shown that HEPES has the least cytotoxicity against all known buffers. At the same time, HEPES is a piperazine-based zwitterionic molecule. Piperazine compounds are derived from phenothiazine. Phenothiazine has been approved by the FDA as an anxiolytic and antipsychotic drug. Non-zwitterionic piperazine compounds have been approved by the FDA as anti-worm agent, other piperazine-based molecules, is approved as a food additive.


Edited by Suzhou Yacoo Science Co., Ltd.