Unilateral radiofrequency lesions or chemical with 6-hydroxydopamine were produced in the substantia nigra of rat brain order to destroy dopaminergic innervations caudate nucleus and thereby produce functional denervation supersensitivity. Both types resulted enhanced stimulation adenylate cyclase (EC 4.6.1.1) activity by dopamine at all concentrations tested, more marked enhancement lower concentrations. Response another agonist, 1-(3,4-dihydroxybenzyl)-4-(20pyrimidinyl) piperazine (S584)...

Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated efficiency a dendrimer-based formulation poorly soluble drug, haloperidol, in targeting via intranasal intraperitoneal administration. Aqueous haloperidol was increased by more than 100-fold developed formulation. Formulation assessed different routes administration for behavioral (cataleptic locomotor) responses, distribution...

The characteristics of mu and delta opioid receptor sites present in human neuroblastoma SH-SY5Y cells were investigated using [D-Ala2-N-methyl-Phe4-Gly-(01)5]enkephalin (DAGO) [2-D-penicillamine, 5-D-penicillamine]enkephalin (DPDPE), which are the most selective radioligands available for sites, respectively. Scatchard analysis saturation isotherms revealed high affinity binding to a single class both [3H]DAGO (mu) [3H]DPDPE (delta). labeled twice number compared capacity [3H]DPDPE,...

An animal model of tardive dyskinesia was used to evaluate the potential antidyskinetic properties neuropeptide L-prolyl-L-leucyl-glycinamide (PLG). In rats, PLG administered concurrently with neuroleptic drug haloperidol or chlorpromazine antagonized enhancement specific [ 3 H]spiroperidol binding in striatum that is associated long-term treatment. The results are discussed relation a possible functional coupling putative receptor neuroleptic-dopamine complex and clinical implications for...

Intranasal (IN) delivery offers potential to deliver antipsychotic drugs with improved efficacy the brain. However, solubilization of such and frequency required re-application both represent challenges its practical implementation in treating various mental illnesses including schizophrenia. Herein, we report a sprayable nanoparticle network hydrogel (NNH) consisting hydrophobically-modified starch nanoparticles (SNPs) mucoadhesive chitosan oligosaccharide lactate (COL) that can gel situ...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDopamine receptor modulation by conformationally constrained analogs of Pro-Leu-Gly-NH2Kuo Long Yu, G. Rajakumar, Lalit K. Srivastava, Ram Mishra, and Rodney L. JohnsonCite this: J. Med. Chem. 1988, 31, 7, 1430–1436Publication Date (Print):July 1, 1988Publication History Published online1 May 2002Published inissue 1 July 1988https://doi.org/10.1021/jm00402a031RIGHTS & PERMISSIONSArticle Views820Altmetric-Citations70LEARN ABOUT THESE METRICSArticle...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBicyclic thiazolidine lactam peptidomimetics of the dopamine receptor modulating peptide Pro-Leu-Gly-NH2Nalin L. Subasinghe, Roger J. Bontems, Edward McIntee, Ram K. Mishra, and Rodney JohnsonCite this: Med. Chem. 1993, 36, 16, 2356–2361Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1 August 1993https://doi.org/10.1021/jm00068a013Request reuse permissionsArticle...

Abstract The role of the hypothalamic tripeptide l‐prolyl‐l‐leucyl‐glycinamide (PLG) in modulating agonist binding to bovine striatal dopamine D 2 receptor was investigated using a selective high‐affinity agonist, n ‐propylnor‐apomorphine (NPA). PLG caused an enhancement [ 3 H]NPA membranes dose‐dependent manner, maximum effect being observed at 10 ‐ 7 6 M concentration tripeptide. Scat‐chard analysis preincu‐bated with revealed significant increase affinity sites. In contrast, there no on...

Neurotrophic factors (NTFs) are important for the development, function, and survival of neurons in mammalian system. Mesencephalic astrocyte-derived neurotrophic factor (MANF) cerebral dopamine (CDNF) two recently identified members a novel family NTFs vertebrates that function to protect dopaminergic neurons. Although these genes conserved across eukaryotes, their mechanism neuroprotection is not fully understood. Sequence searches MANF/CDNF homologs invertebrates have single ortholog most...

The nematode (worm) C. elegans is a leading multicellular animal model to study neuronal-basis of behavior. Worms respond wide range stimuli and exhibit characteristic movement patterns. Here we describe the use microfluidics setup probe neuronal activity that relies on innate response swim toward cathode in presence DC electric field (termed "electrotaxis"). Using this setup, examined mutants affecting sensory dopaminergic neurons found their electrotactic responses were defective. Such...

Abstract The nematode C. elegans is a leading model to investigate the mechanisms of stress-induced behavioral changes coupled with biochemical mechanisms. Our group has previously characterized behavior using microfluidic-based electrotaxis device, and showed that worms display directional motion in presence mild electric field. In this study, we describe effects various forms genetic environmental stress on electrotactic movement animals. Using exposure chemicals, such as paraquat...

ABSTRACT Environmental toxicants such as heavy metals can profoundly impact organismal physiology, yet sensitive and rapid behavioral assays to quantify effects are limited. Here, we employed a microfluidic-based electrotaxis assay systematically evaluate the of chronic exposure metal salts on electrotactic swimming behavior nematode Caenorhabditis elegans . We report that Ag, Hg, MeHg, Cu, Mn, Pb significantly alters speed. Notably, Cu required higher concentrations induce phenotypes,...

Abstract The cDNA expression array is a recently developed scientific tool that can profile the differential of several hundreds genes simultaneously and therefore advantageous in study antipsychotic drug action at genetic level. Using this technology, we discovered 14 rat striatum whose was changed by ≥ 50% following chronic haloperidol treatment. Among them synapsin II gene, which found to be significantly up‐regulated after Since recent studies have implicated gene schizophrenia, further...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and dopamine receptor modulating activity of lactam conformationally constrained analogs Pro-Leu-Gly-NH2Uma Sreenivasan, Ram K. Mishra, Rodney L. JohnsonCite this: J. Med. Chem. 1993, 36, 2, 256–263Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://pubs.acs.org/doi/10.1021/jm00054a010https://doi.org/10.1021/jm00054a010research-articleACS PublicationsRequest reuse...

Bovine striatal dopamine D-2 receptor has been purified approximately 2000-fold by affinity chromatography. The receptor, solubilized with cholic acid and sodium chloride, was adsorbed on haloperidol-linked Sepharose CL-6B eluted spiroperidol. adsorption of to the matrix biospecific as preincubation preparation agonists or antagonists blocked retention receptor. process also displayed stereoselectivity respect (+)- (-)-butaclamol. Nondopaminergic agents such mianserin propranolol failed...