Neurotensin
Neurotensin is a 13-aa neuropeptide in CNS and GI tract that modulates dopamine neurotransmission, reduces pain, regulates gut motility, and has antipsychotic-like properties. Endogenous 'antipsychotic' in dopamine circuits.
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Compound Profile
Neurotensin
Key Data
Research reference only
Research Focus
Preclinical data
⚠ Research & Educational Use Only. Neurotensin is a research chemical documented here for scientific education. All information references peer-reviewed literature and preclinical/clinical study data. Not for human consumption. Not medical advice. Consult a licensed researcher or healthcare professional before any laboratory use.
- Modulates dopamine neurotransmission — acts as an 'endogenous antipsychotic' by reducing dopamine release in mesolimbic circuits
- Analgesic: potentiates opioid analgesia and has independent pain-reducing effects via NTS receptors in the spinal cord
- Reduces core body temperature (hypothermia) via hypothalamic NTS receptors — studied for neuroprotection post-ischemia
- Neurotensin is not FDA-approved for human use. It is a research chemical for scientific study only.
Research At a Glance
- Modulates dopamine neurotransmission — acts as an 'endogenous antipsychotic' by reducing dopamine release in mesolimbic circuits
- Analgesic: potentiates opioid analgesia and has independent pain-reducing effects via NTS receptors in the spinal cord
- Reduces core body temperature (hypothermia) via hypothalamic NTS receptors — studied for neuroprotection post-ischemia
- Promotes satiety and reduces food intake via NTS1 in hypothalamic circuits
In Plain English
Simple summaryNeurotensin is a 13-amino acid neuropeptide distributed throughout the brain (particularly in dopaminergic circuits) and the gut (where it's released in response to fat ingestion). It interacts extensively with the dopamine system -- it modulates dopamine release, is co-released with dopamine in some neurons, and appears to buffer the dopaminergic response to rewards and drugs. In the gut, neurotensin promotes satiety after fat meals and has been identified as one of the signals triggered by fat that contributes to meal termination. The gut neurotensin angle has gotten attention in the context of weight-loss surgery: bariatric procedures that involve the ileum significantly increase postprandial neurotensin levels, and this may contribute to the weight loss benefits beyond caloric restriction.
- Modulates dopamine neurotransmission — acts as an 'endogenous antipsychotic' by reducing dopamine release in mesolimbic circuits
- Analgesic: potentiates opioid analgesia and has independent pain-reducing effects via NTS receptors in the spinal cord
- Reduces core body temperature (hypothermia) via hypothalamic NTS receptors — studied for neuroprotection post-ischemia
The full scientific detail, mechanisms, citations, and dosing data, follows below.
What is Neurotensin?
Tap any underlined term for an instant definition.
Neurotensin (NT) is a 13-amino acid neuropeptide (Glu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu) originally isolated from bovine hypothalamus by Carraway and Leeman in 1973. It is distributed throughout the central nervous system (hypothalamus, limbic system, striatum, spinal cord) and the gastrointestinal tract (ileum L-cells, submucous neurons).
Three neurotensin receptor subtypes have been identified
- **NTS1 (NTSR1)**: High-affinity GPCR (Gq/Gi-coupled); primary mediator of NT's pharmacological effects in brain and periphery
- **NTS2 (NTSR2)**: Lower-affinity GPCR; modulates pain and neurotensin binding in certain brain regions
- **NTS3 (NTSR3/sortilin)**: Single-pass receptor, not a GPCR; involved in protein trafficking and NTS internalization
**Dopamine system interaction — the "endogenous antipsychotic" concept:** Neurotensin co-localizes and co-released with dopamine in mesolimbic neurons. NTS1 activation on dopaminergic neurons reduces their firing rate and dopamine release. This led to the hypothesis that NT is an endogenous modulator of psychotic symptoms — lower NT activity in CSF has been reported in schizophrenia, particularly in dopamine-hyperactive states.
Non-peptide NTS1 agonists have been shown to produce antipsychotic-like effects (reduced amphetamine-induced locomotion, conditioned avoidance responding) in rodent models WITHOUT the extrapyramidal motor side effects of D2 blockers, making NTS1 an attractive target for next-generation antipsychotic development.
**Pain modulation:** Intrathecal NT activates descending pain inhibitory pathways via NTS1 on dorsal horn neurons, producing analgesia comparable to low-dose morphine in some models. Synergy with opioid analgesia has been demonstrated.
**GI and metabolic effects:** NT is secreted by ileal L-cells after fat ingestion (particularly long-chain fatty acids). It slows intestinal transit, modulates gastric acid secretion, and stimulates colonic motility — coordinating the GI response to nutrient absorption. NT also reduces food intake via hypothalamic NTS1, contributing to the satiety response.
By the Numbers
Key Research Benefits
Documented effects observed in preclinical and clinical studies on Neurotensin. See all Cognitive Enhancement peptides for comparison.
Side Effects & Risks
Adverse effects reported in the research literature. All data sourced from preclinical and clinical study reports. View all peptides' side effects →
Dosing Data from the Literature
Doses referenced below are sourced from published preclinical and clinical studies. Use the peptide dose calculator to convert these values to injection volume.
Neurotensin research protocols:
ICV injection (rodent CNS studies): 1-10 nmol for analgesia, hypothermia, and locomotion studies Intraperitoneal/IV: 5-100 nmol/kg for peripheral studies NTS1 agonism research: Non-peptide NTS1 agonists (JMV449, PD149163) with better CNS bioavailability are preferred for behavioral research Schizophrenia drug development: NTS1-selective analogues (NT69L, SR142948A) in preclinical development
Administration in Research Settings
Standard reconstitution and administration methodology for laboratory research use.
Native neurotensin requires ICV, intrathecal, or intracerebral injection for CNS research due to poor BBB penetration. For peripheral research, IV or IP injection is used.
What the research doesn't show
Neurotensin research is active but fragmented across multiple disease areas (schizophrenia, Parkinson's, addiction, obesity) without a clear leading therapeutic application. NTS1 receptor agonists have been studied as antipsychotics with potential reduced side effects, and NTS1 antagonists as weight loss tools -- but neither has led to an approved drug. The biology is rich; the pharmacological translation has been slow.
Medical Expert Videos
Physicians, researchers, and pharmacologists explain Neurotensin, covering mechanisms of action, clinical context, and study findings.
Videos sourced from YouTube search. KnowYourPeptide does not endorse any individual creator. For research education only.
The Bottom Line
Neurotensin has a growing body of preclinical evidence and a well-characterised safety profile in research settings. The most-studied application is: modulates dopamine neurotransmission — acts as an 'endogenous antipsychotic' by reducing dopamine release in mesolimbic circuits.
The most commonly reported side effect in research subjects is hypothermia at pharmacological doses — temperature monitoring required in research protocols. It is a research chemical, not approved for human use.
Frequently Asked Questions
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Quick Reference
How It Compares
Substance P is another neuropeptide in pain and satiety circuits but has different receptor pharmacology. GLP-1, PYY, and CCK are the better-characterized gut satiety peptides -- neurotensin's satiety role is real but less well-defined than these. In the dopamine modulation context, neurotensin has unique properties among gut/brain peptides, as most satiety peptides don't interact as directly with the reward circuitry that drives addictive behavior.
Compare Neurotensin side-by-sideResearch Use Only
This information is for educational research purposes only. This is not medical advice. Consult a qualified healthcare professional.