Sniffing neuropeptides: A transnasal approach to the human brain
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In humans, 40 IU of intranasal vasopressin increased CSF levels from about 5 pg/ml to about 10 pg/ml within 10 minutes and to about 20 pg/ml at 60 minutes.
“Born et al. reported that, after giving 40IU (80µg) in man, CSF levels rose within 10min from ~5pg/ml to ~10pg/ml, increasing to ~20pg/ml at 60min (17).”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [17]
Born et al. achieved plasma vasopressin of 20 pg/ml after 40 IU intranasal, higher than Robertson et al. reported for any patient, including those with pathologically elevated vasopressin; maximal urine concentrating ability in humans occurs at about 5 pg/ml.
“Born et al. achieved plasma concentrations of 20pg/ml after giving 40IU vasopressin (17).These are higher than Robertson et al. reported for any patient, including those with pathologically elevated vasopressin secretion; in man, maximal urine concentrating ability is achieved at a vasopressin concentration of ~5pg/ml (33).”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [17]
In Born et al.'s study, approximately 4.5 ng of vasopressin reached the CSF, representing 0.005% of the administered dose, if the rise came from the administered peptide rather than indirect endogenous release.
“Estimating the CSF volume as 300ml, it seems that ~4.5ng of vasopressin reached the CSF: 0.005% of the given dose -assuming that the rise was due to administered peptide and not endogenous release triggered indirectly.”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [17]
Neuropeptides gain access to the brain following intranasal administration.
“neuropeptides have been shown to gain access to the brain following intranasal administration (Born et al., 2002;Chang et al., 2012).”
From Sex-specific effects of intranasal oxytocin on autonomic nervous system and emotional responses to couple conflict (2013) · cites this paper as Born et al., 2002
Using nasal delivery, substantial amounts of insulin are delivered into the brain.
“Using this delivery route, substantial amounts of insulin are delivered into the brain5”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [5]
The intranasal dose administered in the present study has been associated with changes in central function in humans, and similar or smaller doses of oxytocin or vasopressin have been associated with elevations in peptide levels in the cerebrospinal fluid in humans or macaques of no more than approximately 55 pg/ml or up to 0.005% of the administered dose.
“The intranasal dose administered in the present study has been associated with changes in central function in humans 58, and similar or smaller doses of oxytocin or vasopressin (24–48 IU for oxytocin; 40–80 IU for vasopressin) have been associated with elevations in peptide levels in the cerebrospinnal fluid in humans or macaques of no more than approximately 55 pg/ml in actual levels 70, 71, 72,”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [70]
Many neuropeptides cross the blood-brain barrier when given intranasally.
“Born and colleagues (5) showed that many neuropeptides crossed the blood-brain barrier when given intranasally.”
From Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles (2013) · cites this paper as [5]
Intranasal administration of neuropeptides increases their levels in cerebrospinal fluid.
“Since it was reported that the intranasal administration of neuropeptides increases their levels in cerebrospinal fluid (Born et al., 2002), there has been an upsurge of interest in experimental manipulations of central oxytocin in human populations (Bartz & Hollander, 2006; Campbell 2010; Heinrichs, von Dawans, & Domes, 2009).”
From Acute intranasal oxytocin improves positive self-perceptions of personality (2012) · cites this paper as Born et al., 2002
Peptide concentrations in the cerebrospinal fluid remain relatively stable even 80 minutes after administration.
“It is unlikely that the delay had any impact on the results, as previous research has shown that peptide concentrations in the cerebrospinal fluid remain relatively stable even 80 minutes after administration (Born et al., 2002).”
From Acute intranasal oxytocin improves positive self-perceptions of personality (2012) · cites this paper as Born et al., 2002
It is unlikely that the 90-minute delay had any impact on the results.
“It is unlikely that the delay had any impact on the results, as previous research has shown that peptide concentrations in the cerebrospinal fluid remain relatively stable even 80 minutes after administration (Born et al., 2002).”
From Acute intranasal oxytocin improves positive self-perceptions of personality (2012) · cites this paper as Born et al., 2002
Intranasal administration of neuropeptides can reach the human central nervous system.
“The discovery that intranasal administration of neuropeptides can reach the human central nervous system (17)”
From Oxytocin administration to parent enhances infant physiological and behavioral readiness for social engagement (2012) · cites this paper as [17]
Intranasal administration of vasopressin (AVP) and of OXT increases the intracerebral concentration of these peptides in rats and mice, not only in the cerebrospinal fluid but also in selected brain regions.
“Intranasal administration of vasopressin (AVP) and of OXT have been reported, in rats and mice, to increase the intracerebral concentration of these peptides, not only in the cerebrospinal fluid but also in selected brain regions (Born et al, 2002;Neumann et al, 2013).”
From Chronic and acute intranasal oxytocin produce divergent social effects in mice (2014) · cites this paper as Born et al, 2002
The acute effects of intranasal oxytocin persist until 60-80 min post-administration.
“The acute effects of intranasal oxytocin are reported to persist until 60–80 min post-administration.33, 34”
From Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial (2016) · cites this paper as [33]
Only a small amount of intranasally administered oxytocin reaches the brain.
“It is estimated that only a small amount of intranasally administered oxytocin reaches the brain.33, 34, 46, 47”
From Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial (2016) · cites this paper as [33]
Intranasal administration of peptides bypasses the blood-brain barrier and results in significant cerebrospinal fluid elevations in substance levels within 40 min without systemic infusion.
“The direct manipulation of neuropeptidergic central nervous signaling pathways can be achieved via the intranasal administration of peptides, which is known to bypass the blood–brain barrier and result in significant cerebrospinal fluid elevations in substance levels within 40 min, without the need for systemic infusion (14,15).”
From Oxytocin Reduces Reward-Driven Food Intake in Humans (2013) · cites this paper as [14]
The exact transnasal-CNS route remains unknown, and the proportion of OXT that actually reaches the CNS is exceptionally small relative to the given dose.
“the exact transnasal-CNS route remains unknown, and the proportion of OXT that actually reaches the CNS is exceptionally small relative to the given dose (Born et al., 2002; Chang et al., 2012; Striepens et al., 2013; Dal Monte et al., 2014; Modi et al., 2014).”
From Marmosets treated with oxytocin are more socially attractive to their long-term mate (2015) · cites this paper as Born et al., 2002
Intranasal administration rapidly upregulates OT levels in the brain and plasma during the timeframe of behavioral testing, and OT clears the system several hours after testing.
“These results suggest that intranasal administration rapidly upregulates OT levels in the brain and plasma during the timeframe of behavioral testing, and that OT clears the system several hours after testing.”
From Oxytocin facilitates fidelity in well-established marmoset pairs by reducing sociosexual behavior toward opposite-sex strangers (2014) · cites this paper as Born et al., 2002
Intranasally administered insulin rapidly accumulates in cerebrospinal fluid, indicating efficient transport to the brain.
“Intranasally administered insulin is assumed to travel along olfactory and adjacent pathways and has been shown to rapidly accumulate in cerebrospinal fluid, indicating efficient transport to the brain.”
From Intranasal insulin (2021) · cites this paper as [35]
When acutely administered to humans at cumulative doses up to 200 IU, IN insulin does not lead to large increases in systemic concentrations and appears to trigger side effects such as increases in cortisol and growth hormone only above this threshold.
“When acutely administered to humans at cumulative doses of up to 200 IU, IN insulin does not lead to large increases in systemic concentrations of the hormone 35 and appears to trigger side effects such as increases in cortisol and growth hormone only above this threshold.”
From Intranasal insulin (2021) · cites this paper as [35]
In healthy humans, intranasally administered insulin bypasses the blood-brain barrier and is detectable in cerebrospinal fluid within 1 hour after administration.
“Experiments in healthy humans have shown that IN administered insulin bypasses the BBB and is detectable in CSF within 1 hour after administration.”
From Intranasal insulin (2021) · cites this paper as [35]
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- Authors
- Born, J., Lange, T., Kern, W., McGregor, G. P., Bickel, U., & Fehm, H. L.
- Affiliations
- University of Lübeck (DE)
- Philipps University of Marburg (DE)
- Texas Tech University Health Sciences Center (US)
- Venue
- Nature Neuroscience
- Published
- 2002-05-06
- Volume
- 5
- Issue
- 6
- Pages
- 514-516
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2086190854
- Cited by
- 1,356
- References
- 14
- Citations by year
- 2026: 25 · 2025: 30 · 2024: 42 · 2023: 48 · 2022: 59 · 2021: 75 · 2020: 61 · 2019: 71 · 2018: 67 · 2017: 72 · 2016: 70 · 2015: 86 · 2014: 110 · 2013: 116 · 2012: 77
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- neuropeptides, intranasal drug delivery, blood-brain barrier bypass, cerebrospinal fluid, ACTH4-10, vasopressin, insulin
- MeSH terms
- Administration, Intranasal, Adrenocorticotropic Hormone, Adult, Brain, Female, Humans, Insulin, Male, Osmolar Concentration, Peptide Fragments, Vasopressins
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