Orexin A and Orexin B

Quick Answers About Orexin A and Orexin B

• Is Orexin A and Orexin B FDA approved?

  No. This profile records Orexin A and Orexin B as not FDA approved and for research use only. Review the regulatory and source details on this page for the current context.

• What research supports this Orexin A and Orexin B guide?

  This guide links to 16 curated or current research sources. Inspect the research section and the citations beneath the research answers for their supporting sources.

  Review the Orexin A and Orexin B research sources→

• What are the side effects of Orexin A and Orexin B?

  Reported side effects of Orexin A and Orexin B include Headache and Insomnia (if taken late). They are reported or occasional reactions, not a prediction of what any one person will experience.

• Is Orexin A and Orexin B safe?

  Orexin A and Orexin B has an editorial safety grade of B (Good Safety). Well studied with generally manageable side effects. Safety depends on dose, sourcing, health history and medical supervision, so this page does not call it safe for personal use.

• What is Orexin A?

  Orexin A is a neuropeptide from the lateral hypothalamus that is involved in the regulation of energy balance and peripheral metabolic processes. It is one of two neuropeptides of the orexin (hypocretin) system, along with orexin B, and it acts on the receptors OX1R and OX2R. It is produced by orexinergic neurons, which form a widely projecting population within the lateral hypothalamus.

  • Serum Orexin A and Anthropometric, Hemodynamic and Lipid Profiles in Newly Diagnosed Treatment-Naïve Type 2 Diabetes: a Case-Control Study.
  • The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.
  • Lateral hypothalamic orexinergic neurons as central mediators of pain modulation and non-pharmacological analgesia.

• Where in the body is Orexin B produced?

  Orexin B is synthesized by neurons in the lateral hypothalamus, alongside orexin-A. Orexin-A and orexin-B were originally discovered as hypothalamic neuropeptides. A review reports that orexin B is also expressed in peripheral organs, including the testis, prostate, epididymis, seminal vesicle, and penis, in addition to the hypothalamus. Extra-hypothalamic tissues have been reported to contain orexin-A and orexin-B together with their receptors OX1R and OX2R since the early 2000s.

  • The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
  • Physiological significance of autocrine orexinergic signaling in extra-hypothalamic tissues.
  • Neuroendocrine Control of the Testis: Focus on Orexinergic Modulation of Spermatogenesis.

• What is Orexin B?

  Orexin B (OXB) is a neuropeptide, one of two forms of orexins, which are hypothalamic neuropeptides; the other form is orexin A. Neurons in the lateral hypothalamus synthesize orexin B alongside orexin A, and these neuropeptides are described as orchestrating feeding behavior and energy expenditure. Together with orexin A and their receptors OX1R and OX2R, orexin B makes up the orexin (hypocretin) system, which is primarily known in reviews for its role in sleep-wake regulation and energy homeostasis. A review also describes orexin B as a central orchestrator of arousal and energy homeostasis that is increasingly recognized as a key neuromodulator within the vertebrate retina.

  • Neuroendocrine Control of the Testis: Focus on Orexinergic Modulation of Spermatogenesis.
  • The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.
  • The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.
  • The orexinergic system in the retina: Expression and physiological impact-A review of the literature.

• What role does Orexin A play in energy balance and appetite?

  Orexin A is described as a neuropeptide from the lateral hypothalamus that is involved in the regulation of energy balance and peripheral metabolic processes. Orexin-A is listed, together with cholecystokinin and cocaine and amphetamine-regulated transcript, among essential regulators of various endocrine and autonomic processes, including food intake. In an observational study in humans, the authors proposed that decreased orexin-A levels may be involved in the pathogenesis of Hashimoto's thyroiditis by controlling the thyroid-dependent immune system, insulin resistance, appetite, and body weight.

  • Serum Orexin A and Anthropometric, Hemodynamic and Lipid Profiles in Newly Diagnosed Treatment-Naïve Type 2 Diabetes: a Case-Control Study.
  • Is Hashimoto's Thyroiditis Associated with Insulin Resistance Markers?

• What did studies in rats find about Orexin A and pain relief?

  In rats, Orexin A produced antinociception, meaning a reduction in pain responses. In rats, naloxone pre-treatment significantly attenuated the antinociception evoked by Orexin A, indicating an interaction between Orexin A and opioid signaling. In rats, pre-treatment with the OX1R antagonist SB334867 or the OX2R antagonist TCS OX2 29 markedly reduced the analgesic responses induced by both morphine and Orexin A. A review describes Orexin A and orexin B as acting through the receptors OX1R and OX2R to modulate both the sensory and affective components of pain, with effects that are antinociceptive or pro-nociceptive depending on context.

  • Orexinergic-Opioidergic Interactions Within the Nucleus Accumbens in the Modulation of Acute Pain: Evidence From the Tail-Flick Test in Rats.
  • Lateral hypothalamic orexinergic neurons as central mediators of pain modulation and non-pharmacological analgesia.

• Is Orexin B found outside the brain and hypothalamus?

  Review articles report that, apart from the hypothalamus, orexin B is expressed in peripheral organs including the testis, prostate, epididymis, seminal vesicle and penis. Orexin-A and orexin-B, first discovered as hypothalamic neuropeptides, have since been detected in extra-hypothalamic tissues together with their receptors OX1R and OX2R. A review also describes autocrine orexin signaling in peripheral tissues as a compartment-autonomous mechanism that allows rapid, tissue-specific responses. Orexin peptides, including orexin B, are predominantly produced in the central nervous system, yet circulating orexin peptides are detected in human plasma, and their origin remains an unresolved question.

  • Neuroendocrine Control of the Testis: Focus on Orexinergic Modulation of Spermatogenesis.
  • Physiological significance of autocrine orexinergic signaling in extra-hypothalamic tissues.
  • The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.

• How did Orexin B levels change during sleep deprivation in studies?

  In a human clinical trial, orexin-B turnover increased during sleep deprivation, as measured with a stable isotope labeling kinetics method using mass spectrometry. The same study found no such increase in prepro-orexin turnover, and the authors indicated this points to activity-dependent regulation. A separate human clinical trial reported that sleep deprivation increased all orexin species, including orexin-B, with distinct temporal dynamics across peptide forms.

  • Mass Spectrometry-Based Quantification of Orexin Species in Human Cerebrospinal Fluid Reveals Differential Dynamics Associated with Sleep.

• Has Orexin A shown neuroprotective effects in animal models of brain injury?

  In an animal study using a CLP-induced sepsis-associated encephalopathy model, OXA pretreatment protected against the condition by attenuating oxidative stress, suppressing NF-κB signaling activation, reducing inflammatory responses, and preserving endothelial junction integrity. In that same animal model, OXA pretreatment mitigated blood-brain barrier disruption and improved behavioral performance. A separate description, which does not identify a specific study, states that Orexin-A has demonstrated neuroprotective effects in experimental models of cerebral hypoxia-ischemia.

  • Perioperative orexin-A protects brain microvascular endothelial integrity in experimental sepsis-associated encephalopathy.
  • Temporal profile of serum orexin-A in neonatal hypoxic-ischemic encephalopathy: a prospective longitudinal study.

• Does Orexin B play a role in the stress response?

  Orexin B is described as an excitatory hypothalamic neuropeptide that modulates various stress-related physiological functions. A review states that orexins may influence inflammatory responses through pathways including modulation of the hypothalamic-pituitary-adrenal axis, autonomic nervous system activity, and regulation of adrenal corticosteroid secretion.

  • The impacts of trauma and stress on orexin expression and signalling: A systematic review.
  • The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.

• Did activating the orexin pathway through Orexin A signaling affect depression-like behavior in mice?

  In LH-susceptible mice, chemogenetic activation of the hypothalamic orexin-mPFC pathway alleviated depression-like behaviors through Orexin A signaling. In the same mice, decreased excitatory synaptic transmission in layer V pyramidal neurons of the mPFC was improved by activating hypothalamic orexinergic inputs. That improvement was attenuated by an orexin receptor 1 (OX1R) antagonist, linking it to OX1R signaling.

  • The hypothalamic orexin-medial prefrontal cortex pathway modulates susceptibility to depression in the learned helplessness paradigm in male mice.

• How does Orexin B act through the OX1R and OX2R receptors?

  Orexin B is one of the neuropeptides of the orexin (hypocretin) system and acts through the receptors OX1R and OX2R. A review describes orexin-mediated OX1R signaling as mainly activating the Gq/PLC/IP3/Ca2+ pathway, leading to ERK1/2 and p38 MAPK signaling, while OX2R couples to Gs/Gi, modulating cAMP and PI3K/Akt. In an in vitro study assessed by BRET techniques, orexin B signaling at OX2R was found to be ligand-dependent, G protein-dependent or both. A review of animal studies describes orexins' presynaptic and postsynaptic actions through OX1R and OX2R as complex and often antagonistic, varying by cell type.

  • The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.
  • Physiological significance of autocrine orexinergic signaling in extra-hypothalamic tissues.
  • Orexin receptor 2 (OX2R) exhibits ligand-dependent spatio-temporal pharmacology through Gαi:β-arrestin dynamics in response to Orexin-A and Orexin-B.
  • The orexinergic system in the retina: Expression and physiological impact-A review of the literature.

• Is Orexin A a hormone or a neurotransmitter?

  Orexin A is described as a neuropeptide from the lateral hypothalamus, produced by orexinergic neurons, and involved in regulating energy balance and peripheral metabolic processes. The available facts describe it only as a neuropeptide and do not name it a hormone or a neurotransmitter. In a review of human studies, orexin peptides were detected in human plasma even though they are predominantly produced centrally, and the origin and function of these circulating peptides remain unresolved.

  • Serum Orexin A and Anthropometric, Hemodynamic and Lipid Profiles in Newly Diagnosed Treatment-Naïve Type 2 Diabetes: a Case-Control Study.
  • Lateral hypothalamic orexinergic neurons as central mediators of pain modulation and non-pharmacological analgesia.
  • The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.