This is gonna be a long compilation.
Example:
Brilliant blue g ( http://www.telegraph.co.uk/science/science-news/5921266/Blue-MandMs-mend-spinal-injuries.html )
Just a random news report can lead us to interesting compounds, now this prompts to to look behind its MAO
It acts on P2X7.
Then looking at what acting on that is good for some interesting things came up:
Quote
The P2X7 purinergic receptor: from physiology to neurological disorders
Stephen D. Skaper 1 ,
Patrizia Debetto and
Pietro Giusti
+Author Affiliations
Department of Pharmacology and Anesthesiology, University of Padova, Padova, Italy
1 Correspondence: Department of Pharmacology and Anesthesiology, University of Padova, Largo “E. Meneghetti” 2, 35131 Padova, Italy. E-mail:stephen.skaper@unipd.it
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Abstract
Purine nucleotides are well established as extracellular signaling molecules. P2X receptors are ATP-gated cation channels that mediate fast excitatory transmission in diverse regions of the brain and spinal cord. Several P2X receptor subtypes, including P2X7, have the unusual property of changing their ion selectivity during prolonged exposure to ATP, which results in progressive dilation of the channel pore and the development of permeability to molecules as large as 900 Da. The P2X receptor was originally described in cells of hematopoietic origin, including macrophages, microglia, and certain lymphocytes, and mediates the influx of Ca2+ and Na+ ions, as well as the release of proinflammatory cytokines. P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1β, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7 receptors provides an inflammatory stimulus, and P2X7 receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X7 receptor activity, by regulating the release of proinflammatory cytokines, may be involved in the pathophysiology of depression. The P2X7
receptor may thus represent a critical communication link between the nervous and immune systems, while providing a target for therapeutic exploitation. This review discusses the current biology and cellular signaling pathways of P2X7 receptor function, as well as insights into the role for this receptor in neurological/psychiatric diseases, outstanding questions, and the therapeutic potential of P2X7 receptor antagonism.—Skaper, S. D., Debetto, P., Giusti, P. The P2X7 purinergic receptor: from physiology to neurological disorders.
Quote
J Neurosci. 2010 Jun 9;30(23):8042-7.
Involvement of spinal microglial P2X7 receptor in generation of tolerance to morphine analgesia in rats.
Zhou D, Chen ML, Zhang YQ, Zhao ZQ.
Source
Unit of Pain Research, Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Abstract
Morphine loses analgesic potency after repeated administration. The underlying mechanism is not fully understood. Glia are thought to be involved in morphine tolerance, and P2X(7) purinergic receptor (P2X(7)R) has been implicated in neuron-glia communication and chronic pain. The present study demonstrated that P2X(7)R immunoreactivity was colocalized with the microglial marker OX42, but not the astrocytic marker GFAP, in the spinal cord. The protein level of spinal P2X(7)R was upregulated after chronic exposure to morphine. Intrathecal administration of Brilliant Blue G (BBG), a selective P2X(7)R inhibitor, significantly attenuated the loss of morphine analgesic potency, P2X(7)R upregulation, and microglial activation. Furthermore, RNA interference targeting the spinal P2X(7)R exhibited a similar tolerance-attenuating effect. Once morphine analgesic tolerance is established, it was no longer affected by intrathecal BBG. Together, our results suggest that spinal P2X(7)R is involved in the induction but not maintenance of morphine tolerance.
Quote
Inhibition of the ATP-gated P2X7 receptor promotes axonal growth and branching in cultured hippocampal neurons.
Díaz-Hernandez M, del Puerto A, Díaz-Hernandez JI, Diez-Zaera M, Lucas JJ, Garrido JJ, Miras-Portugal MT.
Source
Departamento de Bioquímica y Biología Molecular IV, Facultad de Veterinaria, UCM, 28040-Madrid, Spain.
Abstract
During the establishment of neural circuits, the axons of neurons grow towards their target regions in response to both positive and negative stimuli. Because recent reports show that Ca2+ transients in growth cones negatively regulate axonal growth, we studied how ionotropic ATP receptors (P2X) might participate in this process. Our results show that exposing cultured hippocampal neurons to ATP induces Ca2+ transients in the distal domain of the axon and the concomitant inhibition of axonal growth. This effect is mediated by the P2X7 receptor, which is present in the growth cone of the axon. Pharmacological inhibition of P2X7 or its silencing by shRNA interference induces longer and more-branched axons, coupled with morphological changes to the growth cone. Our data suggest that these morphological changes are induced by a signalling cascade in which CaMKII and FAK activity activates PI3-kinase and modifies the activity of its downstream targets. Thus, in the absence or inactivation of P2X7 receptor, axons grow more rapidly and form more branches in cultured hippocampal neurons, indicative that ATP exerts a negative influence on axonal growth. These data suggest that P2X7 antagonists have therapeutic potential to promote axonal regeneration.
next example
Pregnenolone (its a male hormone too)
Quote
Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly
Koichi Murakami*,
Arlette Fellous†‡,
Etienne-Emile Baulieu*§, and
Paul Robel*
+Author Affiliations
J F Flood,
J E Morley, and
E Roberts
+Author Affiliations
A A A
Article
References
ABSTRACT | REFERENCES
The therapeutic efficacy of cortisone and pituitary adrenocorticotropic hormone (ACTH)1 in rheumatoid arthritis has suggested the possible application of other steroid hormones in this disease. To this end we have selected Δ5-pregnenolone because of (a) its possible role as a precursor of more active steroid hormones2; (b) its effect on decreasing fatigue3; (c) its sparing action on the adrenal cortex3 and (d) its lack of toxicity in both animals4 and man.5 Davidson and Koetz6 have already commented favorably on its possible value in ankylosing spondylarthritis. In addition, its efficacy by mouth7 has decided advantages to the patient over the parenteral administration necessary with pituitary adrenocorticotropic hormone or cortisone.
SUBJECTS AND METHODS The patients selected for the study presented definite evidence of rheumatoid arthritis according to the standards of the New York Rheumatism Association as presented in the article by Steinbrocker,
Quote
Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence
C.E. Marxa, b, c, 
, 
, ,
D.W. Bradforda, b, c,
R.M. Hamerd,
J.C. Naylora, b, c,
T.B. Allena, b, c,
J.A. Liebermane,
J.L. Straussa, b, c,
J.D. Kiltsa, b, c
a Duke University Medical Center, Durham, NC, USA
b Durham Veterans Affairs Medical Center, Durham, NC, USA
c VA Mid-Atlantic Mental Illness, Research, Education, and Clinical Center
d University of North Carolina, Chapel Hill, NC, USA
e Columbia College of Physicians and Surgeons, New York, NY, USA
http://dx.doi.org/10.1016/j.neuroscience.2011.06.076, How to Cite or Link Using DOI
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Abstract
Emerging preclinical and clinical evidence suggests that pregnenolone may be a promising noveltherapeutic candidate in schizophrenia. Pregnenolone is a neurosteroid with pleiotropic actions in rodents that include the enhancement of learning and memory, neuritic outgrowth, and myelination. Further,pregnenolone administration results in elevations in downstream neurosteroids such as allopregnanolone, a molecule with neuroprotective effects that also increases neurogenesis, decreases apoptosis and inflammation, modulates the hypothalamic-pituitary-adrenal axis, and markedly increases GABAA receptor responses. In addition, pregnenolone administration elevates pregnenolone sulfate, a neurosteroid that positively modulates NMDA receptors. There are thus multiple mechanistic possibilities for pregnenolone as a potential therapeutic agent in schizophrenia, including the amelioration of NMDA receptor hypofunction (via metabolism to pregnenolone sulfate) and the mitigation of GABA dysregulation (via metabolism to allopregnanolone). Additional evidence consistent with a therapeutic role for pregnenolone in schizophrenia includes neurosteroid changes following administration of certain antipsychotics in rodent models. For example, clozapine elevates pregnenolone levels in rat hippocampus, and these increases may potentially contribute to its superior antipsychotic efficacy [Marx et al. (2006a) Pharmacol Biochem Behav 84:598–608]. Further, pregnenolone levels appear to be altered in postmortem brain tissue from patients with schizophrenia compared to control subjects [Marx et al. (2006c) Neuropsychopharmacology 31:1249–1263], suggesting that neurosteroid changes may play a role in the neurobiology of this disorder and/or its treatment. Although clinical trial data utilizing pregnenolone as a therapeutic agent in schizophrenia are currently limited, initial findings are encouraging. Treatment with adjunctive pregnenolone significantly decreased negative symptoms in patients with schizophrenia or schizoaffective disorder in a pilot proof-of-concept randomized controlled trial, and elevations in pregnenolone and allopregnanolone post-treatment with this intervention were correlated with cognitive improvements [Marx et al. (2009)Neuropsychopharmacology 34:1885–1903]. Another pilot randomized controlled trial recently presented at a scientific meeting demonstrated significant improvements in negative symptoms, verbal memory, and attention following treatment with adjunctive pregnenolone, in addition to enduring effects in a small subset of patients receiving pregnenolone longer-term [Savitz (2010) Society of Biological Psychiatry Annual Meeting New Orleans, LA]. A third pilot clinical trial reported significantly decreased positive symptoms and extrapyramidal side effects following adjunctive pregnenolone, in addition to increased attention and working memory performance [Ritsner et al. (2010) J Clin Psychiatry 71:1351–1362]. Future efforts in larger cohorts will be required to investigate pregnenolone as a possible therapeutic candidate in schizophrenia, but early efforts are promising and merit further investigation.
Methylene blue is a known example:
http://www.sciencedaily.com/releases/2008/08/080818101335.htm
Quote
Dopamine-Independent Locomotor Actions of Amphetamines in a Novel Acute Mouse Model of Parkinson Disease
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Abstract
Introduction
Results
Discussion
Materials and Methods
Supporting Information
Acknowledgments
Author Contributions
References
Tatyana D. Sotnikova1, Jean-Martin Beaulieu1, Larry S. Barak1, William C. Wetsel2, Marc G. Caron1*, Raul R. Gainetdinov1
2 Psychiatry and Behavioral Sciences, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina, United States of America
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Brain dopamine is critically involved in movement control, and its deficiency is the primary cause of motor symptoms in Parkinson disease. Here we report development of an animal model of acute severe dopamine deficiency by using mice lacking the dopamine transporter. In the absence of transporter-mediated recycling mechanisms, dopamine levels become entirely dependent on de novo synthesis. Acute pharmacological inhibition of dopamine synthesis in these mice induces transient elimination of striatal dopamine accompanied by the development of a striking behavioral phenotype manifested as severe akinesia, rigidity, tremor, and ptosis. This phenotype can be reversed by administration of the dopamine precursor, L-DOPA, or by nonselective dopamine agonists. Surprisingly, several amphetamine derivatives were also effective in reversing these behavioral abnormalities in a dopamine-independent manner. Identification of dopamine transporter- and dopamine-independent locomotor actions of amphetamines suggests a novel paradigm in the search for prospective anti-Parkinsonian drugs.
Etc
Thread needs ton of work and a clean formatting.