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1.
Eur J Clin Pharmacol ; 55(9): 619-24, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10638388

ABSTRACT

OBJECTIVE: To study the influence of food intake on electrocardiogram (ECG) variables (heart rate, QT-, QTc-, PR-intervals, QRS-time) and morphological alterations of the T-waves in 12 healthy male volunteers. METHODS: The study was of open, three-period crossover design. On each occasion, all subjects fasted from midnight. During two of the study periods, the subjects were given a standardised meal at 1.5 h and 5.5 h after the baseline assessments, respectively, whereas, during the third period, they remained fasting for the entire study period of about 9 h. ECG and blood pressure were recorded at baseline and thereafter every hour for 8 h. RESULTS: No ECG changes were observed following the fasting condition, whereas a clear change in ECG and an increased heart rate were recorded in response to the meal intake during the other two periods. The most prominent ECG effect was the change in the size and shape of the T-waves, which were described as flattened to biphasic and, occasionally, negative. These alterations were most pronounced in the precordial leads V4 to V6 in the ECG recording immediately following the meal intake, with a gradual return to baseline conditions over 4-5 h. Moreover, a transient increase of supine systolic blood pressure was also recorded in response to the meal intake. CONCLUSIONS: The intake of a meal can cause clear and consistent ECG changes in healthy male subjects, comprising increases in heart rate as well as alterations in the size and shape of the T-waves (flattened to biphasic and, occasionally, negative). Also, a post-meal increase in the supine systolic blood pressure was recorded.


Subject(s)
Eating/physiology , Electrocardiography , Heart/physiology , Adult , Blood Pressure/physiology , Cross-Over Studies , Heart Conduction System/physiology , Heart Rate/physiology , Humans , Male , Reference Values , Time Factors
2.
Crit Rev Neurobiol ; 9(2-3): 115-36, 1995.
Article in English | MEDLINE | ID: mdl-8581979

ABSTRACT

Although a large and still increasing number of neuroactive peptides have been discovered in the mammalian brain over the years, it has been difficult to link most of these molecules with specific brain functions and/or brain diseases. A lack of pharmacological tools has hampered the study of brain peptide systems and the elucidation of which among these systems have retained important physiological functions through phylogenesis. Neuropeptide Y (NPY) is one the most abundant neuropeptides in the mammalian brain. A combination of basic and clinical studies has made it possible to circumvent some of these difficulties and provides evidence for a role of NPY in the control of endocrine hypothalamic and pituitary functions, in hypothalamic control of food intake and circadian rhythm, and in limbic emotional integration. Of particular interest is NPY's unique action as an endogenous anxiolytic and its possible role in clinical states of anxiety and depression. Here, we review the biology, anatomy, and physiology of central NPY systems and studies of these systems in various disease states.


Subject(s)
Brain/physiology , Neuropeptide Y/physiology , Animals , Anxiety/physiopathology , Depression/physiopathology
3.
Sleep ; 15(6): 519-25, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1475566

ABSTRACT

Delta sleep-inducing-peptide (DSIP) has been reported to increase sleep in subjects with insomnia. The authors studied cerebrospinal fluid (CSF) DSIP-like immunoreactivity (DSIP-LI) in 15 drug-free male subjects with a DSM-IIIR diagnosis of schizophrenia. The subjects underwent a lumbar puncture and three nights of polysomnography. CSF DSIP-LI was significantly correlated with polysomnography the night before the LP: with stage 3 sleep (p = 0.05), stage 3 and delta (stages 3 + 4) sleep during the first nonrapid eye movement NREM period (p = 0.02 and p = 0.05, respectively) and the ratio of the first and second NREM period (p < 0.05), and negatively with stage 2% sleep (p < 0.05). Whether this first report of a potential relationship between CSF DSIP-LI and slow-wave sleep in man might be generalized to sleep in nonpsychiatric subjects awaits further study.


Subject(s)
Delta Rhythm , Delta Sleep-Inducing Peptide/cerebrospinal fluid , Schizophrenia/cerebrospinal fluid , Schizophrenic Psychology , Sleep Stages/physiology , Adult , Humans , Male , Polysomnography , Radioimmunoassay , Reaction Time/physiology , Schizophrenia/diagnosis , Sleep, REM/physiology , Wakefulness
4.
Neuropeptides ; 22(2): 111-6, 1992 Jun.
Article in English | MEDLINE | ID: mdl-1357579

ABSTRACT

The somatostatin-like (SLI), the neuropeptide Y-like (NPY-LI), and the beta-endorphin-like (BE-LI) immunoreactivities of cerebrospinal fluid (CSF) obtained by suboccipital puncture, or plasma from patients suffering from common migraine or other neuropsychiatric disorders were analysed. The SLI concentration was tendentiously decreased in the migraine patients during the attack-free period compared to that of a 'mixed neuropsychiatric group'. During the migraine attack the level of SLI was further decreased. Similar alteration was found in the CSF BE-LI, while the BE-LI in the plasma showed only a tendentious decrease in common migraine patients. The NPY-LI did not change during the attack period in the CSF or plasma. These findings may indicate the possible role of somatostatin in the pathogenesis of common migraine, and support earlier observations that beta-endorphin is involved in the development in this disorder.


Subject(s)
Migraine Disorders/cerebrospinal fluid , Neuropeptide Y/cerebrospinal fluid , Somatostatin/cerebrospinal fluid , beta-Endorphin/cerebrospinal fluid , Adult , Female , Humans , Male , Middle Aged , Migraine Disorders/blood , Neuropeptide Y/blood , Radioimmunoassay , Somatostatin/blood , beta-Endorphin/blood
5.
J Psychiatry Neurosci ; 17(1): 23-7, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1349825

ABSTRACT

Concentrations of Neuropeptide Y-like (NPY-LI) immunoreactivity in cerebrospinal fluid (CSF) were measured in a group of depressed patients (n = 24) and compared with that of control subjects (n = 12). CSF-NPY-LI was significantly reduced in the group of non-endogenously depressed patients when classified according to Newcastle Rating Scale for Depression--1971 (N-II). No significant correlation was found in the control or depressed groups between lumbar concentrations of NPY-LI and a number of other neurotransmitters.


Subject(s)
Depressive Disorder/cerebrospinal fluid , Neuropeptide Y/cerebrospinal fluid , Adult , Aged , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Female , Humans , Male , Middle Aged , Neurotransmitter Agents/cerebrospinal fluid , Psychiatric Status Rating Scales , Radioimmunoassay
6.
Eur Neuropsychopharmacol ; 1(2): 165-8, 1991 May.
Article in English | MEDLINE | ID: mdl-1821705

ABSTRACT

The concentrations of monoamines and various neuropeptides were determined in the hypothalamus of brains from patients with Alzheimer's disease and vascular dementia (n = 26) and compared with control values (n = 21). Decreased concentrations of 5-hydroxyindoleacetic acid (P less than 0.05) and homovanillic acid (P less than 0.01) were found, and increased arginine vasopressin- (P less than 0.01), galanin- (P less than 0.05) and somatostatin- (P less than 0.01) like immunoreactivity. It is proposed that this disequilibrium may be important for certain circadian symptoms, e.g. the changes in sleep/wake rhythms that are rather often observed in dementia.


Subject(s)
Biogenic Monoamines/metabolism , Dementia/metabolism , Hypothalamus/metabolism , Neuropeptides/metabolism , Aged , Alzheimer Disease/metabolism , Dementia, Vascular/metabolism , Female , Humans , Male
7.
Acta Psychiatr Scand ; 83(4): 273-7, 1991 Apr.
Article in English | MEDLINE | ID: mdl-1709331

ABSTRACT

Postmortem investigations were performed in brains from 14 schizophrenic patients and 21 controls matched for age and autopsy latency. Concentrations of galanin, delta-sleep-inducing peptide (DSIP), corticotropin-releasing factor (CRF), arginine vasopressin (AVP), neuropeptide Y (NPY) and peptide YY (PYY) were determined in the hypothalamus and grey matter from the temporal cortex. A significant positive correlation between age and the concentrations of galanin and CRF was found in the controls. No sex differences were found except a higher mean of CRF in the hypothalamus of the women. In the temporal cortex of the schizophrenic brains, galanin, AVP, NPY and PYY were significantly reduced. DSIP reduction only bordered on significance. CRF was not reduced. Comparing neuroleptic-treated vs non-treated schizophrenics, the treatment factor could not explain the reduced concentrations of neuropeptides in the temporal lobe. A comparison of controls with schizophrenics showed no significant differences in hypothalamic neuropeptide concentrations.


Subject(s)
Hypothalamus/chemistry , Neuropeptides/analysis , Schizophrenia/metabolism , Temporal Lobe/chemistry , Age Factors , Aged , Aged, 80 and over , Antipsychotic Agents/therapeutic use , Arginine Vasopressin/analysis , Corticotropin-Releasing Hormone/analysis , Delta Sleep-Inducing Peptide/analysis , Female , Galanin , Hospitalization , Humans , Hypothalamus/metabolism , Male , Middle Aged , Neuropeptide Y/analysis , Peptide YY , Peptides/analysis , Schizophrenia/drug therapy , Temporal Lobe/metabolism
8.
Regul Pept ; 32(2): 193-201, 1991 Feb 01.
Article in English | MEDLINE | ID: mdl-1674615

ABSTRACT

Classical antipsychotic drugs, such as haloperidol, have been shown to increase the concentrations of neurotensin (NT) selectively in the nucleus accumbens and caudate nucleus of the rat. Several novel, putative antipsychotic drugs have also been found to produce increases in NT content in one or both of these brain regions. The present study sought to compare the effects of chronic treatment with three clinically efficacious atypical antipsychotic drugs, sulpiride, rimcazole and remoxipride, on regional brain NT concentrations to those of haloperidol. The concentrations of NT in five discrete brain regions were determined by a sensitive and specific radioimmunoassay. As previously reported, haloperidol increased NT concentrations in both the nucleus accumbens and caudate nucleus. Sulpiride and rimcazole produced significant increases in the concentration of NT in the caudate. NT concentrations were unaltered in any brain region by remoxipride at either of the doses tested. These data provide additional evidence for specific increases in regional brain NT concentrations produced by antipsychotic drugs.


Subject(s)
Antipsychotic Agents/pharmacology , Caudate Nucleus/metabolism , Neurotensin/metabolism , Nucleus Accumbens/metabolism , Animals , Benzamides/pharmacology , Carbazoles/pharmacology , Caudate Nucleus/drug effects , Haloperidol/pharmacology , Male , Nucleus Accumbens/drug effects , Radioimmunoassay , Rats , Rats, Inbred Strains , Remoxipride , Sulpiride/pharmacology
9.
Psychopharmacology (Berl) ; 103(1): 46-9, 1991.
Article in English | MEDLINE | ID: mdl-1672458

ABSTRACT

The pharmacokinetics of remoxipride, a new selective dopamine-D2 receptor antagonist with antipsychotic action, was evaluated in eight elderly psychiatric patients with tardive dyskinesia (TD). The daily oral doses of remoxipride were gradually increased from 50 mg per day to 200 mg t.i.d. over 2 weeks. The pharmacokinetics following the initial 50 mg dose (day 1) and the last 200 mg dose (day 15) of the drug were compared in serial samples. Plasma prolactin concentrations were assessed at the same time points. The area under the total plasma concentration versus time curves (AUC) of remoxipride increased proportionally with dose from day 1 to 15. The mean "dose corrected" AUC values for the total concentrations were 96.8 at day 1 (4 X 24.2, 50 mg single oral dose) and 92.2 mumol.h/l at day 15 (200 mg). The unbound fraction of remoxipride calculated on AUC was slightly higher on day 15 (20%) than on day 1 (15%) (P less than 0.05), indicating slightly concentration-dependent protein binding of the drug. The mean elimination half-life of total remoxipride was slightly longer on day 15 than day 1 (7.5 versus 5.3 h, P less than 0.01) The corresponding half-lives for the unbound concentrations were 6.4 and 3.9 h, respectively (P less than 0.01). The pharmacokinetics of remoxipride is similar in these TD patients and in non-TD patients in previous studies. Following repeated administration of remoxipride, tolerance to the prolactin-releasing action of remoxipride is observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Antipsychotic Agents/pharmacokinetics , Benzamides/pharmacokinetics , Dyskinesia, Drug-Induced/metabolism , Prolactin/blood , Aged , Antipsychotic Agents/pharmacology , Benzamides/pharmacology , Female , Humans , Male , Middle Aged , Remoxipride
10.
Brain Res Bull ; 25(3): 411-3, 1990 Sep.
Article in English | MEDLINE | ID: mdl-1981332

ABSTRACT

The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.


Subject(s)
Multiple Sclerosis/cerebrospinal fluid , Neuropeptide Y/cerebrospinal fluid , Somatostatin/cerebrospinal fluid , Adult , Humans , Iodine Radioisotopes , Radioimmunoassay
11.
Acta Psychiatr Scand ; 82(2): 95-114, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2173355

ABSTRACT

Neuropeptide Y (NPY) was first discovered and characterized as a 36-amino-acid peptide neurotransmitter in 1982. It is widely distributed in the central nervous system, with particularly high concentrations within several limbic and cortical regions. A number of co-localizations with other neuromessengers such as noradrenaline, somatostatin, and gamma-aminobutyric acid have been demonstrated. A large number of physiological and pharmacological actions of NPY have been suggested. Recent clinical data also suggest the involvement of NPY in several neuropsychiatric illnesses, particularly in depressive and anxiety states. This article gives a comprehensive review of central distribution of NPY and its receptors, co-localizations and interactions with other neuromessengers, genetic aspects, pharmacological and physiological actions, influence on neuroendocrine functions, and possible involvement in various neuropsychiatric illnesses.


Subject(s)
Behavior, Animal/physiology , Brain/physiopathology , Neurocognitive Disorders/physiopathology , Neuropeptide Y/physiology , Receptors, Neurotransmitter/physiology , Synaptic Transmission/physiology , Animals , Brain Mapping , Humans , Receptors, Neuropeptide Y
12.
Neuropeptides ; 16(4): 181-6, 1990 Aug.
Article in English | MEDLINE | ID: mdl-1703283

ABSTRACT

The effects of intracerebroventricularly (icv) administered somatostatin28(SS28) fragments, SS28(1-12) and SS28(15-28), were investigated on central monoaminergic neurotransmission in rats. SS28(15-28) did not significantly influence the hypothalamic and striatal noradrenaline concentrations. In a dose-related manner, SS28(15-28) significantly increased the dopamine, dihydroxyphenyl acetic acid DOPAC), and serotonin concentrations in hypothalamus, but did not modify these measures in striatum. The other SS28 metabolite, SS28(1-12), had no statistically significant effects on the monoamine neurotransmission. SS28(15-28) (6 and 9 nmol) induced barrel rotation, while SS28(1-12) was ineffective following administration over a wide dose-range (3-18 nmol). In conclusion, SS28(15-28) influences the hypothalamic monoaminergic transmission and causes barrel rotation, whereas SS28(1-12) has no neurochemical or behavioural effects in these tests.


Subject(s)
3,4-Dihydroxyphenylacetic Acid/metabolism , Cerebral Ventricles/physiology , Corpus Striatum/metabolism , Dopamine/metabolism , Hypothalamus/metabolism , Norepinephrine/metabolism , Peptide Fragments/pharmacology , Serotonin/metabolism , Somatostatin/analogs & derivatives , Somatostatin/pharmacology , Synaptic Transmission/drug effects , Animals , Cerebral Ventricles/drug effects , Corpus Striatum/drug effects , Hydroxyindoleacetic Acid/metabolism , Hypothalamus/drug effects , Injections, Intraventricular , Male , Motor Activity/drug effects , Peptide Fragments/administration & dosage , Rats , Rats, Inbred Strains , Reference Values , Somatostatin/administration & dosage , Somatostatin-28
13.
Arch Int Pharmacodyn Ther ; 305: 140-51, 1990.
Article in English | MEDLINE | ID: mdl-2241425

ABSTRACT

In a passive avoidance test, intracerebroventricular administration (post-trial treatment) of the somatostatin-depleting compound cysteamine decreased the avoidance latency of the rats in a dose-related manner, while the effect of pantethine (which is metabolized to cysteamine) was less pronounced. In open-field studies, both compounds decreased the motor activity (ambulation, rearing) of the animals 15 min after the injection followed by a subsequent recuperation of the locomotor depression. Following pantethine, the ambulation increased during the later tests (60 min, 240 min, 24 hr). Cysteamine decreased the noradrenaline and increased the dopamine and dihydroxyphenyl acetic acid content in the hypothalamus, whereas the effects of pantethine were less expressed. Both compounds slightly decreased the striatal noradrenaline and increased the dihydroxyphenyl acetic acid levels at 15 and 60 min after administration. However, contrary to pantethine, 4 hr after treatment with cysteamine, there was a decrease in dihydroxyphenyl acetic acid concentration in this brain region. These findings suggest that both pantethine and cysteamine attenuate passive avoidance latency after intracerebroventricular treatment. The different efficiency of pantethine and its metabolite cysteamine might be connected to the low pantetheinase activity of the brain tissue; however, some direct effects of pantethine cannot be excluded. The different effects of the two compounds on the open-field activity are possibly associated with the diverse effects of the compounds on the striatal dopaminergic neurotransmission.


Subject(s)
Behavior, Animal/drug effects , Brain Chemistry/drug effects , Catecholamines/metabolism , Cysteamine/pharmacology , Pantetheine/analogs & derivatives , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Avoidance Learning/drug effects , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Cysteamine/administration & dosage , Dopamine/metabolism , Dopamine/physiology , Hypothalamus/drug effects , Hypothalamus/metabolism , Injections, Intraventricular , Male , Motor Activity/drug effects , Norepinephrine/metabolism , Pantetheine/administration & dosage , Pantetheine/pharmacology , Psychomotor Performance/drug effects , Rats , Rats, Inbred Strains
14.
Int Clin Psychopharmacol ; 5(2): 125-34, 1990 Apr.
Article in English | MEDLINE | ID: mdl-1974271

ABSTRACT

Single dose and steady-state pharmacokinetics of remoxipride, a new antipsychotic drug, were compared after administration of a controlled release capsule (CR) and an immediate release capsule (IR), both 200 mg and administered b.i.d. Thirteen patients with chronic schizophrenia entered the double-blind 6-week crossover study. Seven were evaluable for investigation of steady-state pharmacokinetics. Fluctuations in plasma remoxipride concentrations decreased considerably after remoxipride CR compared with the IR formulation. The plasma peak concentrations were significantly decreased and the trough values were increased after the CR formulation, although the average concentrations at steady-state were similar. The two formulations were bioequivalent regarding the amount of remoxipride absorbed after repeated dosing. Five out of 13 patients withdrew prematurely from the study because of ineffectiveness or refusal of treatment. Both formulations were well tolerated.


Subject(s)
Antipsychotic Agents , Benzamides/pharmacokinetics , Schizophrenia/blood , Schizophrenic Psychology , Adult , Benzamides/administration & dosage , Benzamides/adverse effects , Capsules , Chronic Disease , Delayed-Action Preparations , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Prolactin/blood , Psychiatric Status Rating Scales , Randomized Controlled Trials as Topic , Remoxipride , Schizophrenia/drug therapy
15.
Brain Res ; 507(1): 65-8, 1990 Jan 15.
Article in English | MEDLINE | ID: mdl-2302581

ABSTRACT

Studies on humans and rats have suggested that neuropeptide Y (NPY) is involved in major depression and anxiety. Therefore, we conducted the present study in order to elucidate the effect of repeated (13 or 14 days) treatment of rats with electroconvulsive shocks (ECS) on the concentration of NPY-like immunoreactivity (-LI) in various brain regions, adrenals and plasma. In addition, the effect of ECS on 125I-NPY binding was studied in 3 brain regions. The effects of ECS were compared to effects of 3 control treatments: one group not being handled at all during the time period, one group handled like the ECS-group but not receiving shocks, and one group receiving shocks below the threshold for induction of convulsions. The latter group developed behavioral signs reminiscent of the inescapable shock-induced 'learned helplessness' syndrome (a proposed animal model of depression). We found that the concentration of NPY-LI in the frontal and parietal cortex and in the hippocampus were approximately doubled in the ECS-group as compared to the 3 control groups. No changes in NPY-LI were detected in the striatum, hypothalamus, pons, olfactory bulbs or cerebellum, nor in plasma or adrenals. In spite of the marked changes in NPY-LI concentration, the binding characteristics of 125I-NPY in the frontal and parietal cortex and in the hippocampus were similar in all 4 groups of rats. Finally, we confirmed the previous observation that ECS increase [3H]prazosin binding in cortex. In conclusion, ECS treatment increases neocortical and hippocampal NPY-LI concentrations, while leaving 125I-NPY binding unaffected. Subconvulsive shocks were without effect.


Subject(s)
Cerebral Cortex/metabolism , Hippocampus/metabolism , Neuropeptide Y/metabolism , Prazosin/metabolism , Animals , Cerebral Cortex/physiology , Electroshock , Hippocampus/physiology , Immunohistochemistry , Male , Rats , Rats, Inbred Strains
16.
J Neural Transm Gen Sect ; 79(3): 193-208, 1990.
Article in English | MEDLINE | ID: mdl-2297403

ABSTRACT

The effects of centrally administered NPY on the brain monoamine systems were investigated in the rat. Neuropeptide Y (0.2-5.0 nmol), its C-terminal 13-36 amino acid (a.a.) fragment, NPY13-36 (0.4-10.0 nmol), or saline were injected into the right lateral cerebral ventricle of unrestrained rats. After 1 h the animals were decapitated, and the brains were taken out. Two cortical regions ('frontal' and 'parietal'), the striatum, the hypothalamus, and the brain stem were dissected out. The tissue contents of noradrenaline (NA), dopamine (DA) and serotonin (5-HT), as well as of their major metabolites, 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-indole acetic acid (5-HIAA) were measured. The most consistent finding was a dose-related increase of both DA and DOPAC levels after treatment with NPY. This effect was reproduced by NPY13-36 in cortical tissue, whereas, in the sub-cortical regions, NPY13-36 only reproduced the effects of NPY on the DOPAC levels. Less consistent effects were found on the NA systems, in which NA levels showed a tendency to increase following low, and decrease after high doses of NPY. These effects were largely reproduced by NPY13-36. In addition, NPY increased tissue levels of MHPG in frontal cortical tissue in a dose-related manner. The brain 5-HT systems were not affected.


Subject(s)
3,4-Dihydroxyphenylacetic Acid/metabolism , Brain/metabolism , Dopamine/metabolism , Neuropeptide Y/pharmacology , Norepinephrine/metabolism , Peptide Fragments/pharmacology , Phenylacetates/metabolism , Animals , Brain/drug effects , Dose-Response Relationship, Drug , Male , Rats , Rats, Inbred Strains
17.
Article in English | MEDLINE | ID: mdl-2277850

ABSTRACT

1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactin-secreting adenomas) indications in clinical practice. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson's disease, instead of cysteamine) are discussed.


Subject(s)
Central Nervous System Diseases/drug therapy , Central Nervous System/physiology , Cerebrovascular Disorders/drug therapy , Cysteamine/pharmacology , Pantetheine/analogs & derivatives , Alcoholism/drug therapy , Animals , Central Nervous System/drug effects , Cysteamine/therapeutic use , Humans , Pantetheine/pharmacology , Pantetheine/therapeutic use , Parkinson Disease/drug therapy
18.
Pharm Res ; 7(1): 54-8, 1990 Jan.
Article in English | MEDLINE | ID: mdl-2137217

ABSTRACT

To explore the oral absorption of remoxipride, spheres of remoxipride were labeled with indium-111 colloid before coating with a release-controlling ethylcellulose membrane. Since the labeling remained inside the coating, it was suitable as a marker. Eight healthy volunteers were given a single dose of 100 mg remoxipride in 111In-marked spheres as a multiple-unit capsule. The radioactivity and the position of the spheres (microcapsules) were followed externally for 30 hr by gamma scintigraphy. Parallel to this, plasma concentrations were drawn for 48 hr to confirm the extended dissolution and absorption of remoxipride. The hard gelatin, multiple-unit capsule released the microcapsules within the stomach. These were then rapidly emptied into the small intestine, within 0.5-1 hr. There was then an immediate distribution in the upper small intestine before collection in the lower portion, within 2-5 hr. After passing into the large intestine, there was again extended distribution of the microcapsules. A mean Cmax of 2.7 microM remoxipride was achieved 4 hr after drug administration and a mean AUC of 26.1 mumol.L-1.hr was achieved. Judging from the absorption versus time profile, calculated according to the Wagner-Nelson method, and the scintigraphic images, it is concluded that the main absorption occurs from the small intestine. Data from four volunteers, however, indicated a comparatively good absorption also from the large intestine. Due to the good absorption properties, it is reasonable to expect a low variation in the extent of bioavailability of remoxipride after administration in an extended-release, multiple-unit capsule formulation.


Subject(s)
Benzamides/pharmacokinetics , Gastrointestinal Transit , Administration, Oral , Adult , Benzamides/blood , Delayed-Action Preparations , Humans , Indium Radioisotopes , Male , Microspheres , Remoxipride
19.
Article in English | MEDLINE | ID: mdl-1978375

ABSTRACT

1. The tetradecapeptide somatostatin (SS) has a widespread, uneven distribution within several organs including the central nervous system (CNS), with particularly high concentration in the hypothalamus. 2. The SS-related peptides (SS28, SS28(1-12), SS28(15-28)) are originated from the precursor pre-prosomatostatin. 3. SS is suggested to be involved in a large number of CNS functions, locomotion, sedation, excitation, catatonia, body temperature, feeding, nociception, paradoxical sleep, self-stimulation, seizure, learning and memory. 4. SS influences central neurochemical processes. 5. It is possible that SS is related to various neurological and psychiatric illnesses, like Huntington's disease, multiple sclerosis, Parkinson's disease, epilepsy, eating disorders, Alzheimer's disease, schizophrenia and major depressive illness.


Subject(s)
Central Nervous System Diseases/drug therapy , Central Nervous System/physiology , Somatostatin/pharmacology , Animals , Brain Chemistry/drug effects , Central Nervous System/metabolism , Central Nervous System Diseases/physiopathology , Humans , Somatostatin/metabolism , Somatostatin/therapeutic use
20.
Pharmacol Biochem Behav ; 35(1): 165-70, 1990 Jan.
Article in English | MEDLINE | ID: mdl-1969162

ABSTRACT

In this study the dose- and time-related effects of pantethine on open-field behavior and central neurotransmissions were investigated in rats. Pantethine administered in low doses (0.48-0.96 mM/kg SC) only marginally influenced the activity of the animals, but induced a significant decrease of hypothalamic noradrenaline level without influencing the concentrations of dopamine and DOPAC. Injected in higher doses (1.95-3.90 mM/kg SC), the compound produced a marked depression of both open-field activity and noradrenaline levels, but increased the concentrations of dopamine and DOPAC in the hypothalamus. Twelve hr after the administration of the substance, its effect was attenuated, and 24 hr after the treatment neither the behavioral nor the monoamine parameters differed significantly from the control values. Concerning the somatostatin, pantethine administered in high doses (1.95-3.90 mM/kg SC) decreased the striatal concentration of somatostatin 4 hr after the injection, and this effect was attenuated 24 hr after the treatment. These data suggest that the pantethine-induced behavioral changes are correlated with its effect on central catecholaminergic and somatostatinergic transmission.


Subject(s)
Brain/drug effects , Exploratory Behavior/drug effects , Neurotransmitter Agents/metabolism , Pantetheine/pharmacology , Sulfhydryl Compounds/pharmacology , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Brain/metabolism , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dopamine/metabolism , Dose-Response Relationship, Drug , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Norepinephrine/metabolism , Pantetheine/analogs & derivatives , Radioimmunoassay , Rats , Rats, Inbred Strains , Somatostatin/metabolism , Time Factors
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