Receptors In Central Nervous System Research Articles

Air- breathing in fish: Air- breathing organs and control of respiration: Nerves and neurotransmitters in the air-breathing organs and the skin

In fishes, exploitation of aerial gas exchange has evolved independently many times, involving a variety of air-breathing organs. Indeed, air-breathing occurs in at least 49 known families of fish (Graham, 1997). Many amphibious vertebrates, at some stage of their development are actually trimodal breathers that use various combinations of respiratory surfaces to breath both water (skin and/or gill) and air (skin and/or lung). The present review examines the evolutionary implications of air-breathing organs in fishes and the morphology of the peripheral receptors and the neurotransmitter content of the cells involved in the control of air-breathing. Control of breathing, whether gill ventilation or air-breathing, is influenced by feedback from peripheral and/or central nervous system receptors that respond to changes in PO2, PCO2 and/or pH. Although the specific chemoreceptors mediating the respiratory reflexes have not been conclusively identified, studies in water-breathing teleosts have implicated the neuroepithelial cells (NECs) existing in gill tissues as the O2 sensitive chemoreceptors that initiate the cardiorespiratory reflexes in aquatic vertebrates. Some of the air-breathing fishes, such as Protopterus, Polypterus and Amia have been shown to have NECs in the gills and/or lungs, although the role of these receptors and their innervation in the control of breathing is not known. NECs have been also reported in the specialized respiratory epithelia of accessory respiratory organs (ARO’s) of some catfish species and in the gill and skin of the mudskipper Periophthalmodon schlosseri. Unlike teleosts matching an O2-oriented ventilation to ambient O2 levels, lungfishes have central and peripheral H+/CO2 receptors that control the acid-base status of the blood.

The Neurocognitive Effects of Ghrelin-induced Signaling on the Hippocampus: A Promising Approach to Alzheimer's Disease.

The communication between the gastrointestinal tract and the central nervous system (CNS) allows for certain peptide hormones to influence neurocognitive function. Ghrelin, also known as the ‘hunger hormone,' has the unique ability to enter the CNS and interact with the growth hormone secretagogue receptor (GHS-R) within the hippocampus. Upon interaction with ghrelin, a conformational change in the receptor causes an increase in transcription factors to foster a wide array of physiologic changes in response to caloric deprivation. With the GHS-R in a relatively high concentration within the hippocampus, ghrelin can promote memory, spatial, learning, and behavioral effects. In fact, ghrelin appears to also have a neuroprotective and neuromodulatory response once active within the hippocampal dentate gyrus. Through the GHS-R, higher levels of ghrelin may alter cognitive circuitry and offer a possible link to the treatment of some pathologies implicated in neurological dysfunction. Alzheimer’s disease (AD) is already becoming a significant target for ghrelin neuroreceptor therapy. In such experimental models, ghrelin has been shown to combat this degenerative process by eliciting an ameliorative and regenerative response. Although trials and research are still ongoing, further studies are indicated as early research into this adjuvant therapy is promising.The research team explored the effects of ghrelin by reviewing the downstream signaling modifications of ghrelin's interaction with a specific CNS receptor, the GHS-R. Although the GHS-R is found in multiple locations within the CNS, the team investigated the role of the GHS-R within the hippocampus to focus solely on the neurocognitive implications of ghrelin. The team noted which signaling pathways in particular that ghrelin initiated and used this approach to determine whether ghrelin may have any therapeutic benefits. The team explored the possible therapeutic indications of ghrelin by looking at studies conducted with a specific neurodegenerative disease known to target the hippocampus.

Abstract P205: Age-dependent Alteration in Expression of Brain-derived Neurotrophic Factor and its Receptors in Central Nervous System of Spontaneously Hypertensive Rats.

Background and Aim: Essential hypertension is a cause unknown disease leading to heart disease, stroke and renal failure. Spontaneously hypertensive rats (SHR) are animal model of human essential hypertension and develop hypertension at 7-15-week-old. Several studies reported expression pattern of brain-derived neurotrophic factor (BDNF) changes in central nervous system (CNS) in SHR, suggesting that BDNF and its receptors might be related to increased blood pressure. However, age-dependent change in BDNF and receptors (TrkB and p75NTR) remains to be elucidated. This study aimed to clarify it. Method: Isolated brain tissues from SHR and control Wistar Kyoto Rats (WKY) at 4-, 7- and 15-week-old were dissected into five regions (cerebral cortex: CC; cerebellum: CB; brainstem: BS; hypothalamus: HT; hippocampus: HC). Protein and mRNA expression of BDNF, TrkB isoforms (FL, T1 and T2) and p75NTR as well as an inflammatory marker NOX-2 was examined by Western blotting and real-time PCR. Results: The following data showed significant difference in SHR compared with WKY (n = 4): pro-BDNF protein was lower by 49.9% (4-week, p < 0.05) and 38.2% (7-week, p < 0.05) in HT, while mature BDNF protein was lower by 21.9% in HC (15-week, p < 0.05). TrkB FL mRNA was higher by 32.5% in CB (7-week, p < 0.05) and 43.1% in BS (7-week, p < 0.05), while TrkB FL protein was higher by 51.4% in BS (15-week, p < 0.05). TrkB T1 mRNA was higher by 22.8% in BS (7-week, p < 0.05) and 17.2% in HT (15-week, p < 0.05), while TrkB T1 protein was higher by 56.1% in BS (4-week, p < 0.01). p75NTR protein was higher by 46.9% in CB (7-week, p < 0.05). NOX-2 mRNA was higher by 29.1% (4-week, p < 0.01), 104.2% (7-week, p < 0.01) and 75.8% (15-week, p < 0.05) in CC, 27.0% in CB (15-week, p < 0.05), 34.6% in BS (4-week, p < 0.05), 326.1% in HT (15-week, p < 0.01) and 29.8% in HC (7-week, p < 0.05). Conclusion: We for the first time revealed age-dependent changes in expression of BDNF and its receptors in CNS of SHR. Specifically, our results suggest that alteration of BDNF and TrkB expression is already occurred at juvenile before a stable blood pressure increase. The upregulation of NOX-2 was also identified. Further detailed study might identify whether and how BDNF-receptor-oxidative stress axis is related to pathogenesis of essential hypertension.

The expression and distribution of a leptin receptor in the central nervous system, digestive organs, and gonads of the giant freshwater prawn, Macrobrachium rosenbergii

In the present study, the presence and distribution of leptin receptor (LEP-R) in central nervous system, digestive organs, gonads of giant freshwater prawn, Macrobrachium rosenbergii, were investigated with Western blot and immunohistochemistry. By Western blot a LEP-R with a molecular weight (MW) of 100 kDa was detected in the brain, thoracic ganglia, abdominal ganglia, hepatopancreas, all parts of the gastrointestinal tract, ovaries, and testes. In hepatopancreas and foregut, another intense positive band was detected at molecular weight of 30 kDa, which could be an isotype of LEP-R. By immunohistochemistry, LEP-R-ir was detected in the neurons, and neuropils in the brain, thoracic ganglia, and abdominal ganglia. In the gastrointestinal tract, there was intense LEP-R-ir in the apical part of the epithelial cells of the foregut, midgut, and hindgut. In addition, LEP-R-ir was found in the Restzellen(R)cells and Fibrillenzellen(F) cells in the hepatopancreas. In the ovary, LEP-R-ir was detected in early stage of oocytes and mature oocytes. Intense LEP-R-ir was observed in spermatogonia and spermatocytes of the small and orange claw male prawns. In addition, LEP-R was seen in the high epithelium of spermatic ducts from all male morphotypes. In summary, the detection of the LEP-R-ir suggests the existence of a LEP-R in several organs of M. rosenbergii. Through binding with leptin peptide, LEP-R may be an important signaling molecule that has critical functions in modulating and controlling food intake, energy expenditure, and reproduction in this prawn.

Establishment of an in vitro screening model of bioactive compounds from Vietnamese medicinal plants using the recombinant central nervous system receptors

The central nervous system receptors are important targets of the drugs, involved in many neurological diseases. Therefore, this study was designed to build an in vitro screening model using recombinant receptors distributed in the central nervous system (CNS). Method: construction of cDNA system encoding for receptors; using Semliki Forest virus for the rapid and high expression of receptors in mammalian cell lines; designing binding assays for in vitro pharmacological studies of compounds and methanol plant extracts. Results: 24 cDNAs encoding for receptors and 1 screening kit with neurokinin-1 receptor were constructed; 4 receptors were expressed successfully. Conclusion: The in vitro screening model was established successfully and applied for NK1 receptors with high sensitivity and specificity. This model is a useful tool for discovery and development of target compounds acting in the CNS. 
 Keywords
 Recombinant CNS receptors, an in vitro screening assays, bioactive compounds, Semliki Forest virus. specificity
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Influence of δ-opioid receptor in the central nervous system

The delta-opioid receptor (DOR), which is a classic analgesic drug widely existed in the central system and peripheral system, is a kind of inhibitory G-protein coupled receptor with seven transmembrane regions. In addition to pain modulation, the opioid receptors are involved in various physiological and pathological activities through gene or cytokines. This review addresses the influence and possible mechanisms of the delta-opioid receptor in ischemic brain injury, analgesia, anti-anxiety and depression, learning and memory, and Parkinson's disease. Key words: Receptors, opioid, delta; Central nervous system; Central nervous system diseases; Review

Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy?

Migraine is a neurovascular disorder that involves activation of the trigeminovascular system and cranial vasodilation mediated by release of calcitonin gene-related peptide (CGRP). The gold standard for acute migraine treatment are the triptans, 5-HT1B/1D/(1F) receptor agonists. Their actions are thought to be mediated through activation of: (i) 5-HT1B receptors in cranial blood vessels with subsequent cranial vasoconstriction; (ii) prejunctional 5-HT1D receptors on trigeminal fibers that inhibit trigeminal CGRP release; and (iii) 5-HT1B/1D/1F receptors in central nervous system involved in (anti)nociceptive modulation. Unfortunately, coronary arteries also express 5-HT1B receptors whose activation would produce coronary vasoconstriction; hence, triptans are contraindicated in patients with cardiovascular disease. In addition, since migraineurs have an increased cardiovascular risk, it is important to develop antimigraine drugs devoid of vascular (side) effects. Ditans, here defined as selective 5-HT1F receptor agonists, were developed on the basis that most of the triptans activate trigeminal 5-HT1F receptors, which may explain part of the triptans' antimigraine action. Amongst the ditans, lasmiditan: (i) fails to constrict human coronary arteries; and (ii) is effective for the acute treatment of migraine in preliminary Phase III clinical trials. Admittedly, the exact site of action is still unknown, but lasmiditan possess a high lipophilicity, which suggests a direct action on the central descending antinociceptive pathways. Furthermore, since 5-HT1F receptors are located on trigeminal fibers, they could modulate CGRP release. This review will be particularly focussed on the similarities and differences between the triptans and the ditans, their proposed sites of action, side effects and their cardiovascular risk profile.

A novel ensemble decision tree classifier using hybrid feature selection measures for Parkinson's disease prediction

Parkinson's disease and Alzheimer's disease are the most critical health issues in current days. In neurology, Parkinson disease affects the dopamine receptors of central nervous system. It affects the movement of patients. Dopamine cells are degenerated in this disease progressively, which leads to rapid growth of severity. Extensive amount of research works were done since years for prediction of Parkinson's disease in the early stage. Till date, there is no significant approach, which will provide optimised performance for prediction. Alzheimer's disease is another neurological disease, which generally leads to dementia in most cases Machine learning approaches are more promising approaches for the prediction of these above-said diseases. We presented a novel ensemble-based feature selection measure and decision tree model to predict Parkinson's disease. Experimental results proved that the proposed model has high computational accuracy and true positive rate compared with traditional feature selection measures and ensemble decision trees.

Analysis of expression profile of brain-derived neurotrophic factor and its receptors in central nervous system in spontaneously hypertensive rats

Analysis of expression profile of brain-derived neurotrophic factor and its receptors in central nervous system in spontaneously hypertensive rats

Acute Atrial Fibrillation Induced by Organophosphorus Poisoning: Case Report

Organophosphorus poisoning (OPP) remains a major clinical and public health problem in developing countries. OP compounds act as irreversible cholinesterase inhibitors. Toxicity of these compounds leads to cholinergic excess symptoms through the muscarinic, nicotinic, and central nervous system receptors . Cardiac complications include cardiac arrest, pulmonary oedema, and arrhythmia. Rarely, myocardial infarction has also been reported. Cardiac injury is a strong predictor of death in these patients . We are reporting a case of OP poisoning in a child recently admitted to our facility with acute onset of atrial fibrillation which reverted to sinus rhythm by direct current (DC) cardio version and detoxification of OP component.

Role of GABAA receptor subtypes in the behavioural effects of intravenous general anaesthetics

Since the introduction of general anaesthetics into clinical practice, researchers have been mystified as to how these chemically disparate drugs act to produce their dramatic effects on central nervous system function and behaviour. Scientific advances, particularly during the last 25 years, have now begun to reveal the molecular mechanisms underpinning their behavioural effects. For certain i.v. general anaesthetics, such as etomidate and propofol, a persuasive case can now be made that the GABAA receptor, a major inhibitory receptor in the mammalian central nervous system, is an important target. Advances in molecular pharmacology and in genetic manipulation of rodent genes reveal that different subtypes of the GABAA receptor are responsible for mediating particular aspects of the anaesthetic behavioural repertoire. Such studies provide a better understanding of the neuronal circuitry involved in the various anaesthetic-induced behaviours and, in the future, may result in the development of novel therapeutics with a reduced propensity for side-effects.

Mapping of the prenatal and postnatal methamphetamine effects on D1-like dopamine, M1 and M2 muscarinic receptors in rat central nervous system

Methamphetamine (MA) is worldwide known drug with high potential for addiction that causes dopamine, noradrenaline and serotonin release. MA is also able to increase acetylcholine levels in adult rodents. The aim of this study was to map changes in D1-like dopamine receptors (DR), M1 and M2 muscarinic receptors (MR), and the total number of MR (M1-M5 MR) in the CNS of rats exposed to MA prenatally and in adulthood. Rat mothers were exposed to MA (5mg/kg s.c.) or saline during the entire gestation period and their male offspring were administered in adulthood with single MA (1mg/kg) or saline injection. Thus, the animals were divided into 4 groups: prenatally MA-exposed rats treated with saline (MA/S) or MA (MA/MA) in adulthood and prenatally saline-exposed rats treated with saline (S/S) or MA (S/MA) in adulthood. One hour after the acute treatment animals were sacrificed and their brains were removed. The numbers of M1, M2, total MR, and D1-DR were measured by autoradiography. The main effect was detected in the hippocampus with the most affected M1 MR. D1-DR were decreased in motor cortex and substantia nigra. M1MR were decreased in caudate-putamen, dorsal hippocampus, CA1, CA3 and dentate gyrus (DG). M2MR were decreased in DG only. Total number of MR was moreover decreased in dorsal hippocampus, CA1, CA3 and DG. Our results have shown different patterns of changes in DR and MR, suggesting a pilot role of M1 MR in the CNS changes induced by prenatal and adult MA exposure.

The structure-energy landscape of NMDA receptor gating.

N-methyl-D-aspartate (NMDA) receptors are the main calcium-permeable excitatory receptors in the mammalian central nervous system. The NMDA receptor gating is complex, exhibiting multiple closed, open, and desensitized states; however, the central questions regarding the conformations and energetics of the transmembrane domains as they relate to the gating states are still unanswered. Here, using single molecule Förster Resonance Energy Transfer (smFRET), we map the energy landscape of the first transmembrane segment of the Rattus norvegicus NMDA receptor under resting and various liganded conditions. These results show kinetically and structurally distinct changes associated with apo, agonist-bound, and inhibited receptors linked by a linear mechanism of gating at this site. Furthermore, the smFRET data suggest that allosteric inhibition by zinc occurs by an uncoupling of the agonist-induced changes at the extracellular domains from the gating motions leading to an apo-like state, while dizocilpine, a pore blocker, stabilizes multiple closely packed transmembrane states.

Centrally acting antihypertensive agent Ketanserin potential role in delirium management: A review.

Abstract:Delirium is a psychiatric disorder that is well known for being a clinical challenge due to its complex pathophysiology and the wide range of risk factors associated with it. Up to this date, no medical agent is approved by the Food and Drug Administration (FDA) for the treatment of delirium; despite the fact that, a number of clinical guidelines and protocols have recommended the use of some drugs in the management of delirium. Delirium risk factors; predisposing, hospital and acute underlying disease factors, are considered critical points in understanding delirium mechanism. Furthermore, several pathophysiological hypotheses; neurotransmitters imbalance hypothesis, inflammatory hypothesis and structural defects hypothesis, were introduced to explain delirium pathogenesis. Nevertheless, the current evidence is mainly based on and validates the neurotransmitters imbalance theory, since neurotransmitters form the molecular basis of the central nervous system and can be affected by any change occurs in the brain normal conditions. Moreover, pharmacological options introduced as delirium therapies with relative efficacy are mainly based on the neurotransmitters imbalance theory. Ketanserin is a centrally acting antihypertensive agent that has been in the market for over 30 years from now; thus, safety profile is well established. Ketanserin special and unique mechanism of action by inhibiting a wide range of central nervous system receptors; serotonergic (5-HT1D, 5-HT2B, 5-HT2C, 5-HT6), dopaminergic (D1, D2) and adrenergic (α1, α2) receptors, theoretically seems to match with the pathophysiological hypothesis of neurotransmitters imbalance. Moreover, ketanserin might also serve as an empirical therapy for delirium, when the cause of delirium; other than the underlying medical condition, is not determined and an immediate intervention is needed. As it antagonizes almost all the receptors thought to be associated with delirium. Nevertheless, up to this point, it is still a theoretical assumption about the potential role of ketanserin as a pharmacological option in delirium management that needs further investigations to confirm its efficacy.

Food intake regulation by leptin: Mechanisms mediating gluconeogenesis and energy expenditure.

Regulation of blood glucose levels and body fat is critical for survival. Leptin circulates freely in blood and controls body weight and food intake mainly through hypothalamic receptors and regulates glucose metabolism in the liver both directly through leptin receptors and indirectly via the hypothalamic receptors of central nervous system. Leptin affects food intake regulation and eventually glucose metabolism, lipometabolism, endocrine and immune functions, reproductive function, adipose tissue metabolism and energy expenditure. Leptin also exerts peripheral effects directly on glucose metabolism and gluconeogenesis. Most of obese human subjects have elevated plasma levels of leptin associated to the size of their total adipose tissue mass. Hence gluconeogenic function may be an essential factor in the regulation of nutritional intake and weight gain. The aim of this review is therefore to identify and module the possible effects of leptin with special application in gluconeogenesis. In addition, this review includes the study of fat consumption and energy expenditure in the body. Specific modulation of leptin receptors and adipose tissues functioning could have important inference on therapeutic strategies.

Syntheses, analytical and pharmacological characterizations of the 'legal high' 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo) and analogues.

New psychoactive substances (NPS) are commonly referred to as 'research chemicals', 'designer drugs' or 'legal highs'. One NPS class is represented by dissociative anesthetics, which include analogues of the arylcyclohexylamine phencyclidine (PCP), ketamine and diphenidine. A recent addition to the NPS market was 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo), a morpholine analogue of 3-MeO-PCP. Although suspected to have dissociative effects in users, information about its pharmacological profile is not available. From clinical and forensic perspectives, detailed analytical data are needed for identification, especially when facing the presence of positional isomers, as these are frequently unavailable commercially. This study presents the analytical and pharmacological characterization of 3-MeO-PCMo along with five additional analogues, namely the 2- and 4-MeO-PCMo isomers, 3,4-methylenedioxy-PCMo (3,4-MD-PCMo), 3-Me-PCMo and PCMo. All six arylcyclohexylmorpholines were synthesized and characterized using chromatographic, mass spectrometric and spectroscopic techniques. The three positional isomers could be differentiated and the identity of 3-MeO-PCMo obtained from an internet vendor was verified. All six compounds were also evaluated for affinity at 46 central nervous system receptors including the N-methyl-d-aspartate receptor (NMDAR), an important target for dissociative anesthetics such as PCP and ketamine. In vitro binding studies using (+)-[3-3 H]-MK-801 in rat forebrain preparations revealed moderate affinity for NMDAR in the rank order of 3-Me >3-MeO>PCMo >3,4-MD>2-MeO>4-MeO-PCMo. 3-MeO-PCMo was found to have moderate affinity for NMDAR comparable to that of ketamine, and had an approximate 12-fold lower affinity than PCP. These results support the anecdotal reports of dissociative effects from 3-MeO-PCMo in humans.

11C]AZ10419096 – a full antagonist PET radioligand for imaging brain 5-HT1B receptors

IntroductionThe serotonergic system is widely present in all regions of the central nervous system (CNS) and plays a key modulatory role in many of its functions. Positron emission tomography (PET) is used to study several serotonin receptors in CNS in vivo. The G-protein coupled receptor 5-HT1B is mostly present in the occipital cortex and in midbrain and is linked to several psychiatric disorders. There is evidence that agonist PET radioligands for neuroreceptors are more sensitive to endogenous neurotransmitters than antagonists. Our previously developed 5-HT1B receptor PET radioligand, [11C]AZ10419369, is now considered a partial agonist. In this work we are aiming to develop a full antagonist PET radioligand for imaging brain 5-HT1B receptors, and evaluate its sensitivity to increased endogenous serotonin concentration. Materials[11C]AZ10419096 was synthesized by rapid methylation of the prepared corresponding N-desmethyl precursor with [11C]methyl triflate. Five PET measurements were performed in cynomolgus monkeys, consisting of two at baseline, one after treatment of a monkey with a 5-HT1B antagonist, AR-A000002, and two in which fenfluramine was administered during scanning to induce endogenous serotonin release. Results and discussion[11C]AZ10419096 was synthesized in high yield and purity within 30 min, including purification, formulation and sterile filtration. The baseline PET measurements demonstrated [11C]AZ10419096 to have favorable radioligand characteristics, including high specific binding in brain regions that have high 5-HT1B density, such as occipital cortex and globus pallidus, as well as subsequent rapid elimination from brain and a minor abundance of lipophilic radiometabolites in plasma. AR-A00002 completely blocked radioligand receptor-specific binding. Fenfluramine produced a distinct displacement of radioligand consistent with an expected increase of synaptic endogenous serotonin concentration. Conclusions[11C]AZ10419096, a full 5-HT1B antagonist PET radioligand, demonstrates high specific binding in monkey brain that is sensitive to competition from a known 5-HT1B antagonist as well as to putatively increased endogenous serotonin levels.

Alpha-7 Nicotinic Receptors in Nervous System Disorders: From Function to Therapeutic Perspectives.

The α7 nicotinic receptor consists of identical subunits and is one of the most abundant acetylcholine receptors in the mammalian central nervous system. However its expression is also found in the peripheral nervous system as well as in the immune system and various peripheral tissues. Nicotinic Receptors: They are involved in the regulation of several activities ranging from excitatory neurotransmission, the modulation of the release of several neurotransmitters, regulation of neurite outgrowth, and even neuronal survival/death. Its expression is found in brain areas that underlie learning and memory, suggesting their involvement in regulating cognitive functions. The α7-nicotinic receptor has a strategic role during development in regulating molecular pathways activated during neurogenesis. Because of its pleiotropic effects, receptor dysfunction or dysregulated expression is found in pathophysiological conditions of the nervous system including neurodegenerative diseases and neurodevelopmental disorders. Here we review the physiological and pathological roles of alpha-7 nicotinic receptor in different nervous system disorders and the current therapeutic strategies developed to target selectively this receptor for potentiating or reducing its functions.

Interaction of Plant Extracts with Central Nervous System Receptors.

Background: Plant extracts have been used in traditional medicine for the treatment of various maladies including neurological diseases. Several central nervous system receptors have been demonstrated to interact with plant extracts and components affecting the pharmacology and thereby potentially playing a role in human disease and treatment. For instance, extracts from Hypericum perforatum (St. John’s wort) targeted several CNS receptors. Similarly, extracts from Piper nigrum, Stephania cambodica, and Styphnolobium japonicum exerted inhibition of agonist-induced activity of the human neurokinin-1 receptor. Methods: Different methods have been established for receptor binding and functional assays based on radioactive and fluorescence-labeled ligands in cell lines and primary cell cultures. Behavioral studies of the effect of plant extracts have been conducted in rodents. Plant extracts have further been subjected to mood and cognition studies in humans. Results: Mechanisms of action at molecular and cellular levels have been elucidated for medicinal plants in support of standardization of herbal products and identification of active extract compounds. In several studies, plant extracts demonstrated affinity to a number of CNS receptors in parallel indicating the complexity of this interaction. In vivo studies showed modifications of CNS receptor affinity and behavioral responses in animal models after treatment with medicinal herbs. Certain plant extracts demonstrated neuroprotection and enhanced cognitive performance, respectively, when evaluated in humans. Noteworthy, the penetration of plant extracts and their protective effect on the blood-brain-barrier are discussed. Conclusion: The affinity of plant extracts and their isolated compounds for CNS receptors indicates an important role for medicinal plants in the treatment of neurological disorders. Moreover, studies in animal and human models have confirmed a scientific basis for the application of medicinal herbs. However, additional investigations related to plant extracts and their isolated compounds, as well as their application in animal models and the conducting of clinical trials, are required.

Synthesis and biological evaluation of 99mTc labeled aryl piperazine derivatives as cerebral radiotracers

The aim of this study is to develop cerebral radiotracers for central nervous system receptors imaging. The synthesis, characterization and biological evaluation of two aryl piperazine 99mTc-radiocomplexes based on the piano stool motif [CpM(CO3)] (Cp = cyclopentadienyl, M = 99mTc/Re) is reported. The 99mTc-radiocomplexes were obtained quickly (time < 5 min) with high radiochemical yields. The 99mTc-radiocomplexes characterized by high performance liquid chromatography comparison with the rhenium surrogates have both a suitable lipophilicity and are able to cross the blood brain barrier with 0.43 ± 0.05 and 1.96 ± 0.06% ID/g of brain uptake, at 10 min post injection.