Endomorphin-1

Endomorphin-1's core application potential lies in the field of analgesia. Its analgesic mechanism is similar to that of traditional opioid drugs, but it features a remarkable advantage in reduced side effects, providing a new approach to addressing the clinical dilemma of analgesia. By specifically binding to MOR in the central nervous system (CNS), It initiates pain conduction inhibitory pathways. Particularly in the ventrolateral periaqueductal gray (vlPAG) region of rats, it relieves the tonic inhibition of serotonergic neurons by inhibiting the activity of GABAergic neurons, and enhances the descending pain modulation effect through a disinhibition effect to achieve potent analgesia.

Compared with traditional opioids such as morphine, it's analgesic properties are more clinically attractive. First, it takes effect rapidly with equivalent efficacy: animal experiments have shown that it reaches its analgesic peak 10 minutes after administration, with an analgesic intensity comparable to morphine, and can effectively alleviate acute pain and neuropathic pain. Second, it has significantly reduced side effects: the incidence of life-threatening side effects such as respiratory depression and addiction is far lower than that of traditional opioids, with the risk of respiratory depression reduced by more than 70% compared with morphine.

In recent years, the application value of it in cardiovascular protection has been gradually explored, particularly its groundbreaking potential in the prevention of myocardial ischemia-reperfusion injury (IRI), which has broken the cognitive limitation of it being merely a neuropeptide. MOR is also expressed on the surface of cardiomyocytes, and the product can initiate a myocardial protective mechanism independent of the analgesic pathway by activating this receptor, providing a new target for the emergency treatment and intervention of ischemic heart disease.

In a rat model of 30 minutes of myocardial ischemia followed by 120 minutes of reperfusion, intravenous bolus injection of 50μg/kg the product reduced myocardial infarct size by 35%, while significantly ameliorating myocardial oxidative stress and inflammatory responses: serum levels of the pro-inflammatory cytokines IL-6 and TNF-α decreased by approximately 40%, superoxide dismutase (SOD) activity increased by 1.8-fold, and malondialdehyde (MDA) content decreased by 30%.

Notably, it had no significant effect on heart rate and blood pressure, demonstrating better safety than traditional myocardial protective drugs. Its protective mechanism can be summarized as a three-step cascade reaction: first, activating myocardial MOR to inhibit cAMP overload; second, improving calcium homeostasis to block the opening of the mitochondrial permeability transition pore (mPTP); and finally, attenuating the oxidative-inflammatory cascade and downregulating cardiomyocyte apoptotic signals.

It is widely distributed in brain regions including the nucleus of the solitary tract, hypothalamus and globus pallidus, and is involved in a variety of neurophysiological processes such as mood regulation, reward circuit modulation, autonomic nervous system function regulation and motor control, providing a new perspective for the research of neuropsychiatric diseases and movement disorders. In terms of mood regulation, it binds to MOR in the reward circuit to affect the release of neurotransmitters such as dopamine and serotonin, and participates in the regulation of emotional responses such as pleasure and a sense of accomplishment.

It exhibits a unique role in motor function regulation: bilateral microinjection of it into the globus pallidus of rats induces orofacial movement disorders in a dose-dependent manner, with the effect persisting for 60 minutes without attenuation at the highest dose, indicating that it does not induce desensitization of motor-related receptors. This finding suggests that endogenous it may be involved in the pathogenesis of hyperkinetic movement disorders by continuously activating MOR in the globus pallidus, providing a reference for the pathological research and therapeutic target screening of movement disorders such as Parkinson's disease and chorea.

As a highly selective MOR agonist, it is an indispensable tool peptide in basic scientific research, widely used in MOR function verification, opioid receptor signaling pathway analysis, and research on the mechanisms of pain and neurophysiology. Its well-defined receptor specificity and biological activity provide a standard reference for screening novel opioid ligands and verifying the functions of receptor subtypes, promoting in-depth research on the mechanism of action of opioid drugs.

In 1997, American scientist Zadina and his team first isolated and identified Endomorphin-1-a tetrapeptide (sequence: Tyr-Pro-Trp-Phe-NH₂) with ultrahigh affinity and selectivity for MOR-through systematic screening of mammalian brain tissue extracts. Studies showed that it has a dissociation constant (Ki) of as low as 1.11 nM for MOR, with an affinity for δ or κ receptors that is more than 500-fold lower, demonstrating significantly superior selectivity to traditional endogenous opioid peptides. This discovery challenged the previous notion that endogenous analgesic substances act only through non-selective mechanisms.

Subsequent studies confirmed that it is widely distributed in key pain-regulating regions such as the brainstem, hypothalamus and spinal cord, and its release is increased under painful stimulation. Animal experiments indicated that intracerebroventricular injection of it produces an analgesic effect comparable to morphine but without a ceiling effect (i.e., the analgesic effect continues to enhance with increasing dosage), and its side effects such as addiction and respiratory depression are significantly lower than those of traditional opioids. In addition, it is also involved in cardiovascular regulation (e.g., blood pressure reduction) and immune regulation (e.g., modulating microglial function).