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PubMedDate not supplied

[Behavioural effects of beta-casomorphin-7 in its intranasal administration].

Intranasally administrated natural opioid peptide beta-casomorphin-7 (doses 0.001, 0.005, 0.02, and 0.1 mg/kg) was shown to produce alterations in behavior of male albino rats. The anxiolytic effect of the peptide tested in two "open field" modifications was most pronounced. Besides, two higher doses of promoted learning under conditions of negative reinforcement. The beta-casomorphin-7 effects on pain sensitivity and locomotion were insignificant. The obtained results only in part coincide with the effects of intraperitoneal peptide injection described earlier. This suggests that the specific effects of beta-casomorphin-7 considerably depend on the way of its penetration into a body; in case of intranasal administration they are apparently determined by primarily influence of the peptide on hypothalamic structures.

Administration, Intranasal↗
PubMed1979

[Corticotropic action of a new, synthetic analogue of ACTH (ACTH1-17) in man after intravenous, intramuscular and intranasal administration (author's transl)].

Ala1-lys17-ACTH(1-17)-4-amino-n-butylamide (ACTH1-17), a synthetic analogue of ACTH with shortened amino acid sequence exerts a corticotropic action of at least 8 hours duration in healthy male subjects after either intravenous or intramuscular administration. After intranasal administration of the compound an increased production of cortisol was observed only for three hours. The prolonged action of this new analogue of ACTH following intramuscular administration suggests that it may be of value for therapeutic purposes.

Administration, Intranasal↗
PubMed2006

Sedative effects of midazolam and xylazine with or without ketamine and detomidine alone following intranasal administration in Ring-necked Parakeets.

OBJECTIVE: To evaluate the effects of intranasal administration of midazolam and xylazine (with or without ketamine) and detomidine and their specific antagonists in parakeets. DESIGN: Prospective study. ANIMALS: 17 healthy adult Ring-necked Parakeets (Psittacula krameri) of both sexes (mean weight, 128.83+/-10.46 g [0.28+/-0.02 lb]). PROCEDURE: The dose of each drug or ketamine-drug combination administered intranasally that resulted in adequate sedation (ie, unrestrained dorsal recumbency maintained for >or=5 minutes) was determined; the onset of action, duration of dorsal recumbency, and duration of sedation associated with these treatments were evaluated. The efficacy of the reversal agents flumazenil, yohimbine, and atipamezole was also evaluated. RESULTS: In parakeets, intranasal administration of midazolam (7.3 mg/kg [3.32 mg/lb]) or detomidine (12 mg/kg [5.45 mg/lb]) caused adequate sedation within 2.7 and 3.5 minutes, respectively. Combinations of midazolam (3.65 mg/kg [1.66 mg/lb]) and xylazine (10 mg/kg [4.55 mg/lb]) with ketamine (40 to 50 mg/kg [18.2 to 22.7 mg/lb]) also achieved adequate sedation. Compared with detomidine, duration of dorsal recumbency was significantly longer with midazolam. Intranasal administration of flumazenil (0.13 mg/kg [0.06 mg/lb]) significantly decreased midazolam-associated recumbency time. Compared with the xylazineketamine combination, duration of dorsal recumbency was longer after midazolam-ketamine administration. Intranasal administration of flumazenil, yohimbine, or atipamezole significantly decreased the duration of sedation induced by midazolam, xylazine, or detomidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal administration of sedative drugs appears to be an acceptable method of drug delivery in Ring-necked Parakeets. Reversal agents are also effective when administered via this route.

Administration, Intranasal↗
PubMed2001

Direct nose-brain transport of benzoylecgonine following intranasal administration in rats.

In our previous research, cocaine applied intranasally in rats diffused or was transported directly from the nasal cavity to the brain. However, the direct nose-brain cocaine transport only contributes to an initial increase in the relative cocaine brain exposure. In this study, we have determined the nose-brain transport of a polar metabolite of cocaine, benzoylecgonine, to help understand factors affecting drug transport via this novel pathway. The nasal cavity of male Sprague-Dawley rats was isolated to prevent drainage of nasally applied dosing solution to non-nasal regions. Benzoylecgonine was then administered, either by intranasal administration or by intravenous (iv) injection. At different times postdose, blood and tissues from different regions of the brain were collected from groups of rats (n = 4 for each collection time) and benzoylecgonine concentrations in these samples were analyzed by high-performance liquid chromatography. Benzoylecgonine concentrations in plasma were at maximal levels immediately after iv dosing and declined as a function of time. Following intranasal administration, benzoylecgonine concentrations in plasma reached maximal levels between 15 and 30 min after dosing and declined as a function of time. To allow comparison of brain benzoylecgonine content after iv and intranasal administration, brain benzoylecgonine contents were normalized by plasma benzoylecgonine concentrations. The ratios of the area under the benzoylecgonine concentration-time curve (AUC) between the olfactory bulb and plasma following intranasal administration were 10-100 times higher than those obtained after iv dosing. The olfactory tract-to-plasma benzoylecgonine AUC ratios after intranasal administration were significantly higher than those after iv dosing up to 120 min following dosing. The brain tissue-to-plasma AUC ratios in cerebellum, brain stem, and cerebral cortex after intranasal administration were significantly higher than the corresponding ratios after iv administration up to 30 min following dosing. We conclude than nasally administered benzoylecgonine was transported directly from the nasal cavity to the brain and that the significant increase in brain levels was sustained for a prolonged period of time. Factors contributing to the observed differences in the nose-brain transport of cocaine and benzoylecgonine are discussed.

Administration, Intranasal↗
PubMed1976

Plasma gonadotropin and gonadotropin-releasing hormone levels after intranasal administration of gonadotropin releasing hormone.

Intranasal administration of gonadotropin hormone (GnRH) in doses ranging from 2-4 mg produced a consistently prolonged LH response in patients with secondary amenorrhea. In 4 cases, a delayed secondary rise occurred. A similarly prolonged FSH response was observed in the majority of patients. Six hours after intranasal GnRH, FSH and LH values were well above basal levels and were higher than those observed at a similar interval after intravenous GnRH. Plasma GnRH levels after intranasal administration failed to achieve the high peaks found after the intravenous route but maintained elevated levels for at least an hour and often longer. Despite the much lower plasma GnRH levels, intranasal GnRH produced a sustained effect on LH and FSH secretion, greater than GnRH given by the intravenous route.

Administration, Intranasal↗
PubMed1997

off absorption, pharmacodynamics, metabolism and excretion of 14C-sumatriptan following intranasal administration to the beagle dog.

The pharmacodynamics, pharmacokinetics, metabolism, and excretion of 14C-sumatriptan have been studied in the beagle dog following administration by the intranasal and other routes. The pharmacological response which was monitored, an increase in carotid arterial vascular resistance, correlated with the plasma levels of unchanged sumatriptan following intranasal, intravenous, or intraduodenal administration to the anaesthetised dog. The pharmacokinetics and metabolism of sumatriptan were then confirmed in conscious male and female dogs. Intranasal administration of 14C-sumatriptan resulted in rapid absorption of part of the dose. The overall bioavailability of sumatriptan was 40-50%. Sumatriptan was eliminated from plasma with a half-life of 1.5 or 1.9 h after intravenous or intranasal dosage respectively. Radioactivity was largely excreted in urine (up to 75% of the dose) with small amounts in the bile and faeces after intravenous and intranasal dosing, as sumatriptan and a major metabolite. The results from these studies suggest that intranasal administration provides a viable method for delivering sumatriptan to the systemic circulation.

Administration, Intranasal↗
PubMed2004

Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration.

We investigated the CNS delivery of insulin-like growth factor-I (IGF-I), a 7.65 kDa protein neurotrophic factor, following intranasal administration and the possible pathways and mechanisms underlying transport from the nasal passages to the CNS. Anesthetized adult male Sprague-Dawley rats were given [125I]-IGF-I intranasally or intravenously and then killed by perfusion-fixation within 30 min. Other animals were killed following cisternal puncture and withdrawal of cerebrospinal fluid (CSF) or intranasal administration of unlabeled IGF-I or vehicle. Both gamma counting of microdissected tissue and high resolution phosphor imaging of tissue sections showed that the tissue concentrations and distribution following intranasal administration were consistent with two routes of rapid entry into the CNS: one associated with the peripheral olfactory system connecting the nasal passages with the olfactory bulbs and rostral brain regions (e.g. anterior olfactory nucleus and frontal cortex) and the other associated with the peripheral trigeminal system connecting the nasal passages with brainstem and spinal cord regions. Intranasal administration of [125I]-IGF-I also targeted the deep cervical lymph nodes, consistent with their possible role in lymphatic drainage of both the nasal passages and the CNS. Cisternal CSF did not contain [125I]-IGF-I following intranasal administration. Intravenous [125I]-IGF-I resulted in blood and peripheral tissue exposure similar to that seen following intranasal administration but CNS concentrations were significantly lower. Finally, delivery of IGF-I into the CNS activated IGF-I signaling pathways, confirming some portion of the IGF-I that reached CNS target sites was functionally intact. The results suggest intranasally delivered IGF-I can bypass the blood-brain barrier via olfactory- and trigeminal-associated extracellular pathways to rapidly elicit biological effects at multiple sites within the brain and spinal cord.

Administration, Intranasal↗
PubMedDate not supplied

Kinetics of cocaine in humans after intravenous and intranasal administration.

Cocaine kinetics were studied in four subjects after intravenous and intranasal administration. For intravenous administration cocaine hydrochloride (32 mg) dissolved in physiological saline was injected in 1 ml volume over a 1 min period. Intranasal cocaine was administered as 100 mg powder consisting of an appropriate dose of cocaine hydrochloride (64 and 96 mg) mixed with lactose powder. Subjects were instructed to inhale the mixture through a 5 cm straw within 1 min. Cocaine kinetics, after intravenous injection, conform to a one-compartment open model with first-order elimination. After intranasal administration, cocaine kinetics conform to a one-compartment model with first-order absorption and first-order elimination. The mean half-life of cocaine for intravenous injection in four subjects was 41.4 +/- 8.2 min (mean +/- S.E.M.) and the range was 19 to 64 min. There were statistically significant differences in the mean area under the concentration-time curve (AUC) following intravenous and intranasal administration. The AUC was dose-dependent and the fraction of the dose absorbed after 64 mg intranasal cocaine was significantly lower than after 96 mg dose (p less than 0.05).

Administration, Intranasal↗
PubMed2005

Immediate but not long-term intranasal administration of insulin raises blood pressure in human beings.

Intranasal administration of insulin has been shown to influence neuroendocrine functions via an effect on central nervous mechanisms. Because insulin, in particular when infused into cerebral arteries, induces blood pressure (BP) elevation by an unknown mechanism, we investigated whether insulin exerts similar effects on BP after intranasal administration. To evaluate the immediate effects of insulin on BP, 20 IU of human insulin was intranasally administered every 10 minutes over a 2-hour period. Blood pressure, heart rate, and muscular sympathetic nervous activity (MSNA) were continuously monitored. For evaluating the effects of subchronic administration of insulin, changes during and after 8 weeks of treatment with 160 IU insulin/d on BP were monitored. Compared with placebo, the immediate nasal administration of insulin raised diastolic BP (12.21% +/- 5.10%; P < .05), mean arterial BP (10.81% +/- 4.32%; P < .04), and systolic BP (9.53% +/- 4.66%; P < .08), whereas MSNA and heart rate were unaffected. In contrast, prolonged intranasal insulin administration did not affect BP (P > .62 for all comparisons). The immediate increase in BP in the face of an unsuppressed MSNA after insulin suggests that intranasal insulin transiently changes the baroreflex set point. Thus, data suggest that intranasal insulin administration affects BP regulatory centers in the brain. However, the effect is not observed with prolonged administration of the hormone, suggesting the emergence of counterregulatory processes.

Administration, Intranasal↗
PubMed1996

Effect of intranasal administration of thyrotropin-releasing hormone on ataxic gait in staggerer mice.

The ataxia ameliorating effect of an intranasal administration of thyrotropin-releasing hormone (TRH) was examined using normal and ataxic staggerer mutant mice. In the normal mice, the blood TRH level reached the maximum level 5 min after administration and was gradually eliminated during the following 60 min. The antiataxic effects of TRH in the staggerer mice was examined using an open field method. At lower doses, the intranasal administration of TRH in the staggerer mice was examined using an open field method. At lower doses, the intranasal administration of TRH did not exert any evident effect. However, at 3 mg or 4 mg, the fall index (the ratio of the number of falls to the movement score) was significantly decreased for 20 min after the administration. These results show that an intranasal administration of TRH can ameliorate the ataxia in staggerer mice, and may be promising for clinical use in patients with spinocerebellar degeneration.

Animals↗
PubMed1991

Intranasal administration of neostigmine potentiates both intravenous and intranasal growth hormone (GH)-releasing hormone-induced GH release in short children.

Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release. The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg). In group A (n = 6; age, 10.6-16.0 yr) inNS induced a significant GH increase [inNS vs. saline, area under the curve (AUC; mean +/- SEM), 263.7 +/- 60.2 vs. 73.8 +/- 3.1 micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 +/- 183.0 vs. 644.9 +/- 154.5 micrograms/L.h; P less than 0.03). In group B (n = 6; age, 11.5-15.9 yr) ivGHRH induced a GH rise clearly higher than that induced by inGHRH (604.2 +/- 154.3 vs. 137.1 +/- 28.2 micrograms/L.h; P less than 0.03). Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5 micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/- 103.6 micrograms/L.h; P less than 0.05 and 0.03 vs. inNS and inGHRH, respectively), so that it overlapped with that induced by ivGHRH alone. In conclusion, cholinergic agonists such as neostigmine are able to increase both basal and GHRH-induced GH secretion in short children even when given intranasally. Combined intranasal administration of neostigmine and GHRH (10 micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 microgram/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.

Administration, Intranasal↗
PubMed1993

Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration.

The growth hormone-releasing hormone analogue GHRH(1-29)-NH2 was administered intravenously or intranasally to 30 healthy men aged 19-43 years. Intravenous injection of the lowest dose tested, 0.25 microgram/kg body weight, elicited significant release of growth hormone (GH). Maximal release (mean GH peaks of about 90 mU/l) was obtained with a dose of 1-2 micrograms/kg. Although GHRH(1-29)-NH2 was rapidly eliminated after intravenous injection, GH levels were elevated for about 3 hours. Absorption of GHRH(1-29)-NH2 through the nasal mucosa was found to be low, and the bioavailability was only 3-5%. There was a dose-dependent release of GH after intranasal administration of GHRH(1-29)-NH2, with the maximal response obtained with about 50 micrograms/kg; this dose was approximately as potent as 1 microgram/kg injected intravenously. The GH response after repeated intranasal administration of GHRH(1-29)-NH2 was sustained; there was no suppression of GH secretion during the night following a day when GHRH(1-29)-NH2 had been given three times intranasally. Based on these findings and the obvious convenience of intranasal administration compared with injections, it would be justified to test intranasal therapy for treatment of short stature in children with GH deficiency caused by hypothalamic damage.

Administration, Intranasal↗
PubMed1986

Intranasal administration of alpha-human natriuretic peptide produces a prolonged diuresis in healthy man.

The effects of an intranasal administration of synthetic alpha-human natriuretic polypeptide (alpha-hANP) were studied in 8 healthy male volunteers. They were given an intranasal administration of alpha-hANP at doses of 0.56-0.62 microgram/kg twice in the same day, the first and second administrations being separated by 180 min. Urine volume and urinary sodium excretion increased 2 to 3-fold 60 min after each administration. There were no significant changes in blood pressure, heart rate, glomerular filtration rate, plasma renin activity and plasma concentration of aldosterone, cortisol and catecholamines. The intranasal administration of alpha-hANP was well tolerated by the volunteers, and no untoward effect was observed. The results suggest that alpha-hANP can be used as a nasal spray in patients with overhydration.

Administration, Intranasal↗
PubMed2000

[Studies on melatonin gelatin microspheres for intranasal administration].

AIM: To increase the bioavailability of melatonin (MT), MT gelatin microspheres (MT-GMS) for intranasal administration were prepared. METHODS: MT-GMS were prepared using emulsifying-cross linking technique. Orthogonal tests were used to optimize the preparation conditions. The residence time of technetium-99m (99mTc) labeled gelatin microspheres (GMS) in the nasal cavity of rabbits as compared to gelatin solution, was investigated using gamma scintigraphy. Furthermore the bioavailability in rabbits was examined for evaluating MT-GMS. RESULTS: The mean diameter of MT-GMS was 50.2 microns, the particle size focused on 30-70 microns. The drug content was 13.48%. The release profile in vitro showed sustained effect. The residence time of GMS in the nasal cavity of rabbits was longer than that of gelatin solution. After intranasal administration in rabbits, the bioavailability of MT-GMS was 87.47% as compared to vein injection, while the bioavailability of MT solution was 69.72%. CONCLUSION: MT-GMS prepared could meet the needs of intranasal administration, and could increase the bioavailability of MT.

Administration, Intranasal↗
PubMed1992

Efficacy of intranasal administration of neostigmine in myasthenic patients.

The efficacy of intranasally administered neostigmine was tested in 22 patients with generalized myasthenia gravis (MG). Topical therapy to the highly vascularized oropharynx proved to be quickly effective in 5-15 min both clinically and electrophysiologically. Twenty-eight MG patients were then recruited from different centres and their morning doses of oral pyridostigmine were substituted with intranasal neostigmine over a period of 2 or 3 weeks. Intranasal neostigmine proved to be equally efficacious in this regimen. No side-effect was noted even in 4 patients treated in this way for 1 year. Intranasal administration of anti-acetylcholinesterase may be very beneficial: (1) for patients with irregular absorption of oral doses; (2) early in the morning and every time a fast and temporary effect is needed; (3) in bulbar impairment and emergencies, in which a handy atomizer may be life-saving.

Administration, Intranasal↗
PubMed2004

Intranasal administration of melatonin starch microspheres.

Using melatonin as model drug, starch microspheres for intranasal administration were prepared by an emulsification-crosslinking technique using a uniform design to optimize preparation conditions. The entrapment ratio of melatonin in the microspheres was 11.0% and particle sizes ranged from 30 to 60 microm. Melatonin was released from the microspheres in a sustained manner in vitro. Nasal clearance of 99mTC labeled starch microspheres was investigated using gamma scintigraphy. It was revealed that >80% of the starch microspheres could be detected in the nasal tissue 2h after administration, compared to 30% for a solution. The pharmacokinetics of melatonin starch microspheres was investigated after intranasal administration. The absorption rate was rapid (T(max) min), and the absolute bioavailability was high, 84.07%. A good correlation was found between in vitro release and in vivo absorption data.

Administration, Intranasal↗
PubMed1987

Effects of intranasal administration of atrial natriuretic hormone on spontaneously hypertensive rats.

The effects of the intranasal administration of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) were investigated in 14 anesthetized spontaneously hypertensive rats (SHR; Okamoto-Aoki strain). They were given intranasally synthetic alpha-hANP in distilled water at doses of 10 micrograms/kg, 50 micrograms/kg and 100 micrograms/kg. Intranasal application of 200 microliter of distilled water as a control was also performed in 3 anesthetized SHR. Sixteen anesthetized SHR were examined for the effects of intravenous administration of alpha-hANP at doses of 4 micrograms/kg, 10 micrograms/kg, 20 micrograms/kg and 40 micrograms/kg. Urinary volume and the urinary excretion of sodium increased 2- to 3-fold during the 50 minutes following intranasal administration of a single dose of 50 micrograms/kg or 100 micrograms/kg, although neither the urinary volume nor the urinary excretion of sodium increased after intranasal administration of 10 micrograms/kg of alpha-hANP or 200 microliter of distilled water. There were no significant changes in arterial pressure or heart rate after the intranasal administration of synthetic alpha-hANP or distilled water. In contrast, arterial pressure was decreased and urinary volume and urinary excretion of sodium were increased, in a dose dependent manner, within 5 minutes after intravenous bolus-injection of alpha-hANP and returned to their baseline levels within 20 minutes. These results indicate that intranasal administration of synthetic alpha-hANP exerts its diuretic effect without concomitant changes in arterial pressure or heart rate in SHR.

Administration, Intranasal↗