Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are two primary output pathways from the striatum: a projection to the globus pallidus, and projection to the substantia nigra. Certain striatally expressed neuropeptides are differentially distributed between these two pathways. Specifically, enkephalin is expressed in striatopallidal neurons, whereas substance P and dynorphin are expressed in striatonigral neurons. Several serotonin receptors are also prominently expressed in the striatum, but little is known about how they fit into the molecular neuroanatomy described above. We used double-label in situ hybridization to determine the striatal distribution of the mRNAs of the serotonin2A (5-HT2A), serotonin2C (5-HT2C), and serotonin6 (5-HT6) receptors in relation to enkephalin, substance P, and dynorphin expressing output neurons. Rat brain sections were simultaneously hybridized with an 35S riboprobe for one of the serotonin receptors and a digoxygenin labeled riboprobe for one of the neuropeptides. Sections were examined by using brightfield microscopy, and the degree of colocalization of the two mRNAs determined. All the serotonin receptors colocalized extensively with all three of the neuropeptides examined. None of the serotonin receptors showed preferential colocalization in striatopallidal (enkephalin containing), or striatonigral (substance P or dynorphin containing) cells. The 5-HT2A and 5-HT2C mRNAs displayed a differential distribution with regard to the scattered islands of strongly dynorphin mRNA positive cells, which are thought to reside in the striatal patch compartment. Within these islands, 5-HT2C mRNA expression was much higher than in surrounding areas. 5-HT2A mRNA showed the opposite pattern with decreased expression over dynorphin rich cell clusters.
 ...
PMID:Colocalization of serotonin receptor subtypes 5-HT2A, 5-HT2C, and 5-HT6 with neuropeptides in rat striatum. 879 65

Depression is a highly debilitating disorder that has been estimated to affect up to 21% of the world population. Despite the advances in the treatment of depression with selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), there continue to be many unmet clinical needs with respect to both efficacy and side effects. These needs range from efficacy in treatment resistant patients, to improved onset, to reductions in side effects such as emesis or sexual dysfunction. To address these needs, there are numerous combination therapies and novel targets that have been identified that may demonstrate improvements in one or more areas. There is tremendous diversity in the types of targets and approaches being taken. At one end of a spectrum is combination therapies that maintain the benefits associated with SSRIs but attempt to either improve efficacy or reduce side effects by adding additional mechanisms (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2C, alpha-2A). At the other end of the spectrum are more novel targets, such as neurotrophins (BDNF, IGF), based on recent findings that antidepressants induce neurogenesis. In between, there are many approaches that range from directly targeting serotonin receptors (5-HT2C, 5-HT6) to targeting the multiplicity of potential mechanisms associated with excitatory (glutamate, NMDA, mGluR2, mGluR5) or inhibitory amino acid systems (GABA) or peptidergic systems (neurokinin 1, corticotropin-releasing factor 1, melanin-concentrating hormone 1, V1b). The present review addresses the most exciting approaches and reviews the localization, neurochemical and behavioral data that provide the supporting rationale for each of these targets or target combinations.
 ...
PMID:Innovative approaches for the development of antidepressant drugs: current and future strategies. 1648 68

Olanzapine is an atypical antipsychotic agent of the thiobenzodiazepine class. It blocks multiple neurotransmitter receptors including dopaminergic at D1, D2, D3, D4 brain receptors, serotonergic at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors. Olanzapine has five times the affinity for 5-HT2 receptors than D2 receptors and has been used to treat schizophrenia and delirium. Olanzapine's activity at multiple receptors, particularly at the D2, 5-HT2c, and 5-HT3 receptors which appear to be involved in nausea and emesis, has prompted its use in the treatment of nausea and vomiting refractory to standard antiemetics. Case reports and formal clinical trials have demonstrated its efficacy in the treatment of chronic nausea, the prevention of chemotherapy-induced nausea and emesis, and the treatment of breakthrough chemotherapy-induced nausea and emesis. Phase II and phase III clinical trials have demonstrated that there is a significant improvement in nausea when olanzapine is added to guideline directed prophylactic antiemetic agents 5-HT3 receptor antagonists and tachykinin NK1 receptor antagonists in patients receiving moderately or highly emetogenic chemotherapy Common side effects of olanzapine when used over a period of months include weight gain as well as an association with the onset of diabetes mellitus, but these effects have not been seen with short term use of daily doses of less than one week.
...
PMID:Olanzapine for the prevention and treatment of chronic nausea and chemotherapy-induced nausea and vomiting. 2415 85