bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the possible role of central monoaminergic systems in the central nervous system actions of vinpocetine
Authors: Kiss Béla , Szporny László 
Published: January 2005

AbstractThe effects of vinpocetine, a recently described cerebral blood flow enhancer having antihypoxic, anti‐ischemic, and cognitive‐function‐improving actions, on rat brain monoaminergic neurotransmission have been studied under normoxic and hypoxic conditions. Vinpocetine slightly affected the steady‐state levels of monoamines and their metabolites in whole brain, but a tendency was seen to increase dopamine (DA) and its metabolites in lower brain parts and to reduce noradrenaline (NA) in “terminal” regions. MHPG‐SO4 levels were enhanced in whole brain and in almost all regions examined. There was a tendency to increase 5‐hydroxyindole‐acetic acid (5‐HIAA) in some areas. It accelerated the whole brain NA turnover dose‐dependenntly, but left that of DA unchanaged. Enhancement of NA turnover was most noted in the lower brain areas. On the other hand, no change was found in DA accumulation, an index of heart NA turnover after inhibition of dopamine‐beta‐hydroxylase. The rate of probenecideinduced accumulation of cerebral MHPG‐SO4 and, to a lesser extent, that of 5‐HIAA was also increased. No change was seen in the pargyline‐induced serotonin (5‐HT) accumulation. Although vinpocetine had slight or no effects on regional levels of monoamines and their metabolites, and did not alter their in vivo biosynthesis rate under normoxic conditions, it was able partially or totally to prevent reductions in the biosynthesis rate of monoamines and antagonized the decrease of NA, 5‐HT, and 5‐HIAA (but not that of DA) induced by normobaric hypoxia. This effect was mainly confined to lower brain areas. From the results, we conclude that vinpocetine primarily affects cell body regions (e.g., brainstem) of the rat brain. Enhancement of the activity of ascending noradrengergic and, perhaps, serotoninergic pathways may very likely participate in the cognitive function‐imporving actions of the drug under normoxic conditions. Vinpocetine was able to prevent monoamigergic neurotransmission against deleterious effects of hypoxia.
Effect of nootropic drugs on age‐dependent changes in transmitter release
Authors: Schmidt Joachim , Wustmann Christian , Rudolph Erika , Zschorn Eva‐Maria , Fischer Hans‐Dieter 
Published: January 2005

AbstractDopamine release from rat striatum slices shows marked age‐dependent changes. In 9‐month‐old animals the potassium‐stimulated efflux is reduced by more than one‐half compared with the maximum release seen at an age of 2–6 months. That means that the vesicle storage pool loses its functional maximum size at a relative early age. The mechanisms underlying these changes are complex and unclear as yet. Experimental data show interesting relationships between age‐dependent and hypoxia‐induced changes in cerebral neurotransmission. The posthypoxic changes in transmitter release are prevented by single high doses of nootropics and related drugs, and long‐term treatment with lower, not protective doses leads to a marked acceleration of the restitution. Therefore, we studied the effect of a long‐term treatment of aging rats with nootropics and related drugs. Piracetam meclofenoxate, or vinpocetine given to old rats in low doses twice a day for 3 weeks cause a significant diminution of the age‐dependent lowering of dopamine release. This result leads to the assumption that nootropic drugs retard in part age‐dependent processes in the CNS.
Electrophysiologic effects of vinpocetine and vincamine on isolated rabbit papillary muscle in normal‐ and low‐potassium medium
Authors: Leboeuf J. , Lamar J. C. , Massingham R. 
Published: January 2005

AbstractThe electrophysiologic effects of vinpocetine (VP) on the action potential (AP) of the isolated rabbit papillary muscle were compared with those of vincamine (VC) in normal (5.6 mM)‐ and low (2.7 mM)‐potassium concentrations. In 5.6 mM K+ medium, VC (1 and 10 μM) did not affect the resting potential (RP) but increased AP duration at 50% and 90% of repolarization (APD50 and APD90). At 10 μM, a decrease in maximal depolarization velocity (Vmax) was also observed. Under these conditions, VP (1 and 10 μM) hyperpolarized the RP and at 10 μM increased both Vmax and AP amplitude. VP (1 μM) shortened AP duration at 30% of repolarizaton (APD30), but did not significantly modify APD50 and APD90 at 1 and 10 μM. The effects of VP on APD30, APD50, APD90, and Vmax were significantly different from those of VC. Reducing extracellular K+ from 5.6 to 2.7 mM did not significantly modify the effects of VC on AP, except for the RP, which was hyperpolarized. The changes in RP and Vmax caused by VP (1 μM) in low‐K− medium were significantly different from those caused by the compound in normal‐K+ medium were significantly different from those caused by the compound in normal‐K+ medium. However, the decrease in Vmax and increase in APD30, APD50, and APD90 obtained with VC were significantly different from those seen with VP. VC increased AP duration in both normal‐ and low‐K+ concentration. As such, VC poses the risk of “torsades de pointe” dysrhythmia, associated with a long QT interval, even in patients with normal serum K+ levels. On the other hand, our results indicate that such dysrhythmias are not expected with VP even in patients with hypokalemia.
Effect of vinpocetine on the sleep‐wake cycle of rats
Authors: Sarkadi Adam , Laszy Judit , Szporny Lászlö 
Published: January 2005

AbstractVinpocetine given orally for five consecutive days in weekly, ascending doses produced changes in the sleep‐wake cycle of the rat, as measured by the electrocorticogram. The effect of vinpocetine on the sleep‐wake cycle was interpreted as an increase in alertness, and was most prevalent at the highest dose of 30 mg/kg/day p.o. This effect lasted for two weeks following the discontinuation of the treatment. Hypoxia‐induced sleep disturbances were not improved by daily administration of vinpocetine in rats. These data support three conclusions: (1) vinpocetine may evoke functional and/or metabolic processes in the brain that are related enhanced alertness; (2) within the dose range examined vinpocetine had no “antihypoxic” activity during moderate hypoxic episodes; and (3) the effect of vinpocetine appears to be extended beyond the treatment period.
Variation of muscarinic activities of oxotremorine analogues
Authors: Brown Frank , Clark Michael , Graves Diane , Hadley Michael , Hatcher John , McArthur Robert , Riley Graham , Semple James 
Published: January 2005

AbstractClose analogues of oxotremorine (a potent muscarinic agonist with marked CNS actions) were examined for inhibition of ligand binding in rat cortex membranes using 3H‐oxotremorine‐M and 3H‐quinuclidinyl benzilate, and in simple tests in vivo for autonomic and behavioural effects (induction of salivation, hypothermia, tremor, inhibition of locomotion in mice; inhibition of sparring and rearing behaviours in rats). The combined use of these tests indicated whether compounds were agonists, antagonists, or inactive at muscarinic receptors, and gave preliminary details of their pharmacological profile and selectivity on different muscarinic responses. The analogue known as BM5 was a partial agonist with a selective profile. It was considered of interest for further study as a possible candidate for therapeutic use in the memory impairment (and acetylcholine deficit) of Alzheimer's disease. In studies in tests for long‐term (24‐hr passive avoidance) and short‐term, working (5‐min arena maze) memory/cognition in rats, no evidence of enhancement was obtained with BM5.
Experimentally established geropsychotropic properties of 3‐hydroxypyridine antioxidant
Authors: Voronina T. A. , Kutepova O. A. 
Published: January 2005

AbstractThe free radical hypothesis is one of the most widely accepted theories of aging. In this respect antioxidant agents, stabilizing free radical‐induced damage of biological membranes, can be considered as possible geropsychotropic drugs. Comparative experimental investigation of 3‐ and 18‐month‐old albino male rats demonstrated age‐related functional insufficiency in some behavioural tests in elderly animals. Consumption of the antioxidant 2‐ethyl‐6‐methyl‐3‐hydroxypyridine (3‐HP) (40–75 mg/kg/day) for two months normalized memory function, motor‐skill learning, and motor coordination in 18‐month‐old rats. Furthermore, 3‐HP ingestion during chronic alcohol administration improved learning in alcohol‐treated mice. The beneficial effect of 3‐HP on age‐related and alcohol‐induced decline of memory and learning ability may be due to its ability to increase cell resistance to different disturbing actions.
Comparison of the effects of vinpocetine, vincamine, and nicergoline on the normal and hypoxia‐damaged learning process in spontaneously hypertensive rats
Authors: Groó Dóra , Pálosi Éva , Szporny László 
Published: January 2005

AbstractVinpocetine (Cavinton®), vincamine, and nicergoline (Sermion®) were evaluated for the ability to protect cognitive function of spontaneously hypertensive rats from the damaging effect of hypoxia. Normobaric hypoxia (6% oxygen) was applied during the acquisition of a two‐way active avoidance task (3 sessions, 50 trials/session). Hypoxia decreased the percentage of conditioned avoidance responses by 50% on day 3. Vinpocetine (1.25–10 mg/kg) administered orally 60 min prior to the daily sessions did not significantly improve learning in normoxic conditions; however, it prevented hypoxia‐induced learning deficit (1.25 mg/kg peak effect dose). The dose‐response relationship for the compound is an inverted U‐shaped curve. Vincamine (2.5–20 mg/kg p.o.) did not facilitate learning under normoxic conditions, but afforded protection against hypoxia at the 20‐mg/kg dose. Nicergoline (2.5–20 mg/kg p.o.) did not increase acquisition of the normoxic avoidance response, and it also showed a moderate antihypoxic effect. Vinpocetine, and to a lesser degree vincamine and nicergoline–‐drugs useful in the therapy of cognitive disturbances following cerebral ischemichypoxic states–‐proved effective in the prevention of a hypoxia‐induced learning deficit.
Dextronatrin: A potent atrial natriuretic peptide analog; Vascular and natriuretic effects
Authors: Deghenghi R. , Immer H. U. , Beaulieu G. , Muirhead C. R. 
Published: January 2005

AbstractA shortened 23 amino acid analog (dextronatrin) of rat ANP(1–28) in which, in position 6 next to Cys, there is a D‐Tyr residue, has been compared to rat ANP(1–28) for its diuretic and electrolyte‐excreting properties in male normotensive rats. Both compounds elicited an equally large but short‐lasting diuresis. The natriuresis was also short‐lasting as were the changes in Cl− and K+ excretion.In a rabbit aortic strip preparation dextronatrin antagonized the vasoconstricting effects of noradrenaline but to a lesser extent than rat ANP(1–28).
Current hypotheses of Alzheimer disease neuropathology and dementia
Authors: Wisniewski H. M. , Merz G. S. , Rabe A. , Barcikowska M. , Moretz R. C. , Devine‐Gage E. A. 
Published: January 2005

AbstractImmunology and biochemical studies of paired helical filaments (PHF) revealed the presence of the following proteins: (1) phosphorylated tau, (2) ubiquitin, and (3) neurofilament peptides. Quantitative biochemical studies of the PHF peptides are in progress, and as yet it is not known which of the above proteins or possibly, a novel protein is the initiator and major constitutent of PHF. The peptide‐forming amyloid fibers in the meninges, brain vessels, and neuritic plaques are a product of a host gene localized on chromosome 21. The reason for the formation of the amyloid fibers in normal aged people and in Alzheimer disease is unknown. However, in Down syndrome, it may be a result of a gene dose effect. Imbalance between the production of the amyloid fiber precursor protein and the ability to degrade it may also be the result of gene mutation of the amyloid peptide‐producing cell or a result of an enzyme defect or deficiency of the amyloidogenic peptide processor cells.
Human cerebral amyloidosis
Authors: Frangione Blas 
Published: January 2005

AbstractTwo types of familial cerebral amyloid angiopathy or hereditary cerebral hemorrhage with amyloidosis (HCHWA) have been described: the Icelandic type (HCHWA‐I) and the Dutch type (HCHWA‐D). Both are autosomal‐dominant forms of amyloidosis restricted to the small vasculature of the brain and are clinically characterized by recurrent strokes leading to an early death. In spite of their clinico‐pathological similarities, the amyloid fibrils are structurally different. In the case of HCHWA‐I, the amyloid protein is a degradation product of Cystatin C, a normal serum protein and an inhibitor of cysteine proteases. On the other hand, the amyloid protein in HCHWA‐D has been shown to be related to Alzheimerapos;s disease β‐protein, and preliminary observations indicate that similar amyloid subunits are present in sporadic cerebral amyloid angiopathy and asymptomatic elderly people with amyloidosis. The processing of the β‐protein precursor in different cell types may account for the heterogeneous pattern of clinical manifestations and amyloid deposition in this group of disorders, which we designate “beta‐amayloid diseases.”
Uptake of normal immunoglobins by motor neurons in the rat: A study using radioiodinated IgG
Authors: Fabian Roderic H. 
Published: January 2005

AbstractSprague‐Dawley rats were anesthetized and the mystatial vibrissae was injected with 0.3‐120 pmol of 125I‐labeled affinity‐purified nonspecific rat IgG with and without additional unlabeled IgG in 50 μL of normal saline. Following a survival of 2 days, the rats were deeply anesthetized and perfused with saline and buffered formalin. The brains were removed and punch sample taken that included the facial nuclei. Uptake of radioiodinated IgG by the facial nucleus was determined by subtracting background activity, which was determined from the facial nucleus punch sample contralateral to the injection, from the ipsilateral facial nucleus. Uptake of radiolabeled IgG established a linear relationship with the amount of radiolabeled IgG injected, and only a very small amount was taken up (0.21 fmol per nmol injected). Addition of unlabeled IgG had no effect on the uptake of radiolabeled IgG. This evidence supports immunohistochemical evidence indicating that nonspecific serum IgG is taken up by motor neurons of the CNS with axons projecting the periphery. An increased understanding of this and other aspects of the relationship between the nervous system and the humoral immune system may provide insight concerning the pathogenesis of certain types of autoimmune nervous system disease.
Nervous‐system‐associated mast cells: Gatekeepers of neural and immune interactions
Authors: Orr Edward L. 
Published: January 2005

AbstractAlthough mast cells have been described in or near certain areas of the central and peripheral nervous systems, the present investigation demonstrates that nervous‐system‐associated mast cells in the mouse are strategically located along the vasculature that supply or drain these tissues. Of particular interest are the mast cells present in the velum interpositum of the transverse fissure. These mast cells are distributed along blood vessels that perfuse or drain the thalmus, hippocampal formation, corpus striatum, corpora quadrigemini, and the choroid plexi of the lateral ventricles. Such a distribution suggests that mast cells and their vasoactive products (e.g., histamine, serotonin, leucotrienes) may be involved in regulating the regional permeability of the vessels supplying or draining these important brain regions. In addition, numerous periganglionic mast cells were found to be distributed in and around vessels of the dorsal root ganglia and spinal roots. Consequently, periganglionic mast cells may control the permeability of the blood vessels perfusing or draining the dorsal root ganglia and spinal roots and thereby control the ability of immune components to access these tissues, the spinal cord, and the adjacent subarachnoid space. Thus, nervous‐system‐associated mast cells may serve as cellular gatekeepers of interactions between the immune and nervous systems.
Tritiated D‐ala1‐peptide T binding: A pharmacologic basis for the design of drugs which inhibit HIV receptor binding
Authors: Smith Craig C. , Hallberg Paul L. , Sacerdote Paola , Williams Patricia , Sternberg Esther M. , Martin Brian M. , Pert Candace B. , Ruff Michael R. 
Published: January 2005

AbstractThe HIV virus initiates its infectious cycle through a high‐affinity binding interaction between the envelope protein gp 120 and its receptor, the T4 (or CD4) molecule. An octapeptide sequence, termed peptide T, present in the second variable region of gp 120 from the ARV isolate, has been implicated as the attachement site. The core peptide required for activity has been further refined to a pentapeptide, and homologous pentapeptides are similarly positioned in 21 other sequenced HIV isolates. Utilizing a novel direct binding assay of 3H‐D‐ala1‐peptide T, we now report that synthetic peptides derived from these other isolates are potent competitors of peptide T binding to T4‐positive lymphocytes and brain membranes. Direct peptide T binding is also competable by purified virion gp 120, indicating that these ligands are interactive at the same receptor. Peptide T has sequence relatedness to the peptide vasoactive intestinal peptide (VIP), and VIP and its relevant homologous pentapeptide, VIP[7–11], are also potent inhibitors of peptide T binding. To determine the essential structural features responsible for receptor activity we have studied a series of synthetic peptides substituted with single D‐amino acid residues. These data reveal that the tyrosine of position 7 in peptide T, present in all natural viral isolates, is obligate for receptor activity. Structure/function analysis for a large number of analogs is presented. Significantly, this binding assay is highly correlated with peptide bioactivity in several independent systems, indicating that this methodology can be used for rapid screening of novel, potential anti‐AIDS therapeutics whose target is inhibition of virus gpl20 binding.
Neurochemical profile in vitro of irindalone: A5‐HT2‐receptor antagonist
Authors: Hyttel John , BøGesø Klaus , LembøL Hanne LøVe , Larsen Jens‐JøRgen , Meier Eddi 
Published: January 2005

AbstractA new potential antihypertensive drug, irindalone (Lu 21‐098;(+)‐(1R,3S)‐1‐[2‐[4‐[3‐(p‐fluorophenyl)‐1‐indanyl]‐1‐piperazinyl] ‐ethyl]‐2‐imidazolidinone), has been characterized by a series of in vitro methods. Irindalone competitively inhibits peripheral and central serotonin2 (5‐HT2) receptors as measured by 5‐HT‐induced contractions of rabbit pulmonary artery and receptor binding methodology with 3H‐ketanserin as a ligand. The inhibitory effect on 5‐HT receptors is confirmed using other organs in vitro (rat stomach fundus, rat jugular vein, guinea pig trachea). Irindalone has lower affinity for α1‐adrenoceptors and histamine‐H1 receptors and only negligible affinity for α2‐adrenoceptors and muscarine cholinergic receptors. No inhibition of the uptake of noradrenaline (NA), dopamine (DA), or 5‐HT is seen. The neurochemical profile resembles that of ketanserin, which has slightly higher affinity for 5‐HT2 receptors. In the rat fundus, irindalone inhibits 5‐HT‐induced contractions, differing in this respect from ketanserin and cinanserin. Irindalone clearly deviates from the neuroleptics haloperidol and tefludazine, and from prazosin with which irindalone has been compared. The (‐)enantiomer of irindalone, Lu 21‐099, is considerably weaker than irindalone in the different test systems. Due to the strong blockade of 5‐HT2 receptors and the somewhat weaker blockade of α‐adrenoceptors, irindalone is expected to lower blood pressure potently and thus be a candidate for the treatment of hypertension.
Conditioned response to amphetamine injection with the operant paradigm
Authors: Duncan Perry M. , Barry Theresa , Ellis Roger , Hinkle Elizabeth 
Published: January 2005

AbstractConditioned responses to amphetamine treatment at three doses were investigated with the “conditioned emotional response” paradigm, in which an auditory‐visual stimulus was presented 3 min before i.p. drug injection to rats lever pressing for food pellets. Conditioned responses to this preinjection stimulus were indicated by changes from baseline response rate during each of eight conditioning sessions and after water injections (again preceded by the A‐V stimulus) on a final extinction‐test day. In experiment 1, the reinforcement schedule was tandem VI‐30 sec/FR4, and the amphetamine dose was 3.0 mg/kg, which produced nearly complete response suppression by the end of the 20‐min postinjection period. Suppression to the preinjection CS was seen after two conditioning sessions, and marked condition suppression also occurred after water injection on the test day. In a second experiment, using additional animals, the reinforcement schedule was VI‐60 sec, and two drugged groups were used to determine lower‐dose amphetamine effects. Significant preinjection suppression (of a lesser degree than seen in experiment 1) developed after six conditioning sessions with amphetamine 1.5, but not 0.8 mg/kg. Similar dose differences were seen in the postinjection‐conditioned responses. These results provide dose‐response information on conditioned responses to a CNS stimulant in the conditioned suppression paradigm.
Partial generalization in pigeons trained to discriminate morphine from saline: Applications of receptor theory
Authors: Koek Wouter , Woods James H. 
Published: January 2005

AbstractIn pigeons trained to discriminate 5.6 mg/kg of morphine from saline, cyclazocine, l‐N‐allyl‐normetazocine (l‐NANM, l‐SKF10,047), and ketamine, but not U50,488, produced partial generalization, i.e., a maximum level of drug‐appropriate responding between the levels produced by saline and by the training drug. The generalization gradient of cyclazocine and of l‐NANM, but not that of ketamine, was less steep than the gradient of morphine. Cyclazocine and l‐NANM, but not U50,488 and ketamine, antagonized partially the discriminative stimulus (DS) effects of morphine. Naltrexone antagonized the DS effects of morphine, cyclazocine, and l‐NANM, but not ketamine. Increasing the training dose of morphine shifted the morphine gradient to the right, increased the antagonist effects of cyclazocine and of l‐NANM, and decreased their agonist effects, but did not alter the effects of ketamine. Decreasing the training dose of morphine shifted the morphine gradient to the left and increased the agonist effects of cyclazocine, but did not alter the effects of l‐NANM and ketamine. The full generalization produced by cyclazocine when the training dose of morphine was lowered could be blocked completely by naltrexone and l‐NANM, but not by ketamine. These results suggest that cyclazocine and l‐NANM, but not ketamine, produced partial generalization because of their low efficacy at the receptor that underlies the DS effects of morphine. However, the results obtained with ketamine suggest that partial generalization may also be produced through other mechanisms.