Penetration of DGAVP (Org 5667) across the blood-brain barrier in human subjects

Riekkinen, P.; Legros, Jean-Jacques; Sennef, C.; Jolkkonen, Jukka; Smitz, Simon; Soininen, Hilkka

doi:10.1016/0196-9781(87)90101-x

Cited by 48 publications

(12 citation statements)

References 23 publications

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“…Only in a few studies, intranasally administered substances were determined in humans in the CNS. Their results indicate that the substances can be measured in the CNS within 10 min after intranasal administration [21].…”

Section: Introductionmentioning

confidence: 94%

Time Course of Intranasally Administered Cholecystokinin-8 on Central Nervous Effects

et al. 2001

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The gut and brain peptide cholecystokinin (CCK) exerts a number of central nervous effects. Among them are effects on attention and stimulus processing as revealed by modulations of event-related potentials (ERPs). In the present study the time course of central nervous effects after an intranasal administration of CCK-8 was investigated by means of ERPs. ERPs were recorded in an oddball paradigm 15, 30, 60, 90, 120, and 240 min after administration. Following the double-blind intranasal administration of CCK-8 and placebo, the late positive complex (LPC) of the ERP was significantly increased following CCK-8 compared to placebo. This effect was more pronounced in women than in men. The enhancement of the LPC by intranasal CCK-8 was not restricted to a specific recording time but reached its maximum 120 min after administration in men and women. Moreover, results tentatively indicate that 30 min after administration of CCK-8 the LPC increased only in women but not in men. The early effect of intranasal CCK-8 on LPC in women is unlikely to be caused by changes in plasma CCK-8 levels and suggests a direct nose-brain pathway.

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Section: Introductionmentioning

confidence: 94%

Time Course of Intranasally Administered Cholecystokinin-8 on Central Nervous Effects

et al. 2001

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“…16,17 Moreover, in humans synthetic peptides such as 1-desamino-8d-arginine-vasopressin (DDAVP) have been shown to accumulate in liquor after intranasal administration. 18 There are also coherent functional data indicating a direct access of peptides to brain functions through the nose. 19,20 Here, we compared effects of different doses of ANG II after intranasal versus intravenous administration on plasma vasopressin and catecholamine concentrations, blood pressure, heart rate, and systemic vascular resistance.…”

mentioning

confidence: 99%

Intranasal angiotensin II directly influences central nervous regulation of blood pressure

Derad¹,

Willeke²,

Pietrowsky³

et al. 1998

American Journal of Hypertension

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Intranasal administration of some peptides has been shown to directly influence central nervous functions, thus pointing to a nose-brain pathway for these substances in humans. The present study investigated whether intranasal administration of angiotensin II (ANG II) affects central nervous functions of cardiovascular control in a different way from intravenously administered ANG II. In a balanced cross-over design 12 healthy men were treated with ANG II intravenously (2.5 g), ANG II intranasally (400 g), and placebo. Angiotensin II, vasopressin, norepinephrine, and epinephrine plasma levels were assessed every 10 min; blood pressure, heart rate, and systemic vascular resistance were measured by a Dinamap, and by continuous, noninvasive body plethysmography. Also, feelings of activation and mood were measured. Intranasal and intravenous administration invoked equivalent increases in plasma levels of ANG II, and induced an acute rise in blood pressure of comparable size and duration. However, subsequent blood pressure profiles differed dependent on intravenous and intranasal ANG II administration; after intravenous ANG II administration blood pressure remained enhanced at an intermediate level, but it returned to normal or even decreased below normal levels after intranasal ANG II administration. Intranasal ANG II also counteracted the decrease in norepinephrine levels observed after intravenous administration of ANG II. Intranasal but not intravenous ANG II enhanced plasma concentrations of vasopressin. This diverging pattern of effects bears similarities with effects of intracerebroventricular administration of ANG II in animals, suggesting that the effects after intranasal administration reflect a direct central nervous action of ANG II. Am J Hypertens 1998;11:971-977

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“…In humans, the direct detection of peptides in the brain after intranasal administration is more difficult due to the rather invasive method of assessment. However, intranasally administered insulin and a vasopressin analog were found to accumulate in cerebrospinal fluid at concentrations distinctly higher than would be predicted on the basis of resorption from systemic blood [8]. We also have preliminary data from 2 healthy individuals showing a distinct increase in ACTH concentrations in cerebrospinal fluid within 45 min after intranasal intake of the peptide [Born et al, unpubl.…”

Section: Introductionmentioning

confidence: 90%

“…In two recent trials we also found a corresponding increase in cerebrospinal fluid concentration after intranasal administration of ACTH [Born et al, unpubl. data, 8]. Studies in primates indicated that after intranasal administration larger proteins like horseradish peroxidase can directly enter the brain and cerebrospinal fluid compartment within 45 min [7, 40].…”

Section: Discussionmentioning

confidence: 99%

Brain Potentials and Attention after Acute and Subchronic Intranasal Administration of ACTH 4–10 and Desacetyl-α-MSH in Humans

et al. 1999

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Neuropeptides related to adrenocorticotropin (ACTH) are potent regulators of neurobehavioral functions. In humans, ACTH and its behaviorally active fragment ACTH 4–10 have been consistently found to diminish event-related brain potential (ERP) signs of focussing attention. This study aimed at (1) evaluating effects of ACTH 4–10 on ERP indicators of attention in healthy controls after intranasal administration of the peptide. This route of administration has been proposed to provide a more direct access to the brain than the intravenous administration of the peptide, (2) comparing acute effects and effects of a subchronic treatment with ACTH 4–10, and (3) comparing effects of ACTH 4–10 with those of desacetyl-α-MSH (corresponding to ACTH 1–13 amide) which like ACTH 4–10 binds to subgroups of the melanocortin receptor family. Double-blind placebo-controlled experiments were completed in 54 healthy young subjects. ERPs were recorded while the subject performed an auditory selective attention task. Moreover, a modified Stroop interference test including motivational (food, sex) and nonmotivational words was performed. Acute intranasal administration of ACTH 4–10 (1 mg) reduced the processing negativity (PN) of the ERP over frontal and central cortical areas (p < 0.05) indicating diminished focussing of attention. Moreover, on this condition subjects were more prone to interference on the Stroop task especially with motivational words (p < 0.05). Subchronic administration of ACTH 4–10 (1 mg/day over 6 weeks) did not affect PN and Stroop performance. Acute intranasal administration of desacetyl-α-MSH at equimolar doses (1.68 mg) also remained ineffective. However, some measures of Stroop performance appeared to improve after subchronic desacetyl-α-MSH treatment. Results confirm an acute decrease in focussing of attention after ACTH 4–10. These effects of intranasal administration are likely to reflect a direct action of the peptide on respective brain functions. Moreover, they were specific to ACTH 4–10 and were not obtained after equimolar doses of desacetyl-α-MSH, thus excluding a mediation via the known melanocortin receptors.

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Penetration of DGAVP (Org 5667) across the blood-brain barrier in human subjects

Cited by 48 publications

References 23 publications

Time Course of Intranasally Administered Cholecystokinin-8 on Central Nervous Effects

Time Course of Intranasally Administered Cholecystokinin-8 on Central Nervous Effects

Intranasal angiotensin II directly influences central nervous regulation of blood pressure

Brain Potentials and Attention after Acute and Subchronic Intranasal Administration of ACTH 4–10 and Desacetyl-α-MSH in Humans

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