And schizophrenia

Roth BL, Sheffler DJ, Kroeze WK (2004) Magic shotguns versus magic bullets selectively non-selective drugs for mood disorders and schizophrenia. Nat Rev Drug Discov 3 353-359... 

On the other hand, 5-HT2C agonists are being investigated in obesity, depression, and schizophrenia, and SCA-136, has entered phase II trials in schizophrenia. 

Davies LM, Drummond MF (1994). Economics and schizophrenia. The real cost. Br J Psychiatry 165 (suppl. 25), 18-21. 

Knoble, MB and Weinberger, DR (1997) Dopamine, the prefrontal cortex and schizophrenia. J. 

Schizophrenia and bipolar disorder often share certain symptoms, including psychosis in some patients. The prominence of mood symptoms and the history of mood episodes distinguish bipolar disorder and schizophrenia. In addition, the psychosis of schizophrenia occurs in the absence of prominent mood symptoms. 

Psychogenic dysfunction occurs if a patient does not respond to psychic arousal. It occurs in up to 30% of all cases of ED. Common causes include performance anxiety, strained relationships, lack of sexual arousability, and overt psychiatric disorders such as depression and schizophrenia.5 It is postulated that the anxious or nervous man will have excessive stimulation of the sympathetic system, leading to smooth muscle contraction of arterioles and vascular spaces within erectile tissue.6 O Many patients may initially have organic dysfunction, but develop a psychogenic component as they try to cope with their inability to achieve an erection. It has been estimated that up to 80% of ED cases have an organic cause, with many having a psychogenic component as well.1... 

Joober, R., Benkelfat, C., Brisebois, K. et al. (1999). T102C polymorphism in the 5HT2A gene and schizophrenia relation to phenotype and drug response variability. /. Psych. Neurosci., 24, 141-6. 

Malhotra, A. K., Goldman, D., Buchanan, R.W. et al. (1998). The dopamine D-3 receptor (DRD3) Ser-9Gly polymorphism and schizophrenia a haplotype relative risk study and association with clozapine response. Mol. Psychiatry, 3, 72-5. 

Spurlock, G., Helis, A., Holmas, P. etal. (1998). A family based association study of T 102C polymorphism in 5HT2A and schizophrenia plus identification of new polymorphisms in the promoter. Mol. Psychiatry, 3, 42-9. 

Vogt, I. R., Shimron-Abarbanell, D., Neidt, H. etal. (2000). Investigation ofthehuman serotonin 6 [5HT6] receptor gene in bipolar affective disorder and schizophrenia. Am. J. Med. Genet., 96,217-21. 

Patients tend to believe that medications from nature are non-toxic, non-addicted, and non-invasive. Therefore complementary medicines are usually used in common, less severe, and chronic mental disorders such as sleep disorders, neurasthenia, and anxiety disorders. It is also applied in incurable conditions, for example dementias, autism, and schizophrenia, when doctors and families have tried desperately all means and finally turned to complementary medicine as the last hope. 

Yui, K., Goto, K., Ikemoto, S. et al. Neurobiological basis of relapse prediction in stimulant-induced psychosis and schizophrenia the role of sensitization. Mol. Psychiatry. 4 512, 1999. 

Reserpine A drug extracted from Rauwolfia serpentina which was once clinically used in the treatment of essential hypertension and schizophrenia. 

Andreasson S, Allebeck P, Engstrom A and Rydberg U (1987). Cannabis and schizophrenia A longitudinal study of Swedish conscripts. Lancet, 2, 1483-1486. 

Ishiguro H, Okuyama Y, Toru M, Ari-nami T. Mutation and association analysis of the 5 region of the dopamine D3 receptor gene in schizophrenia patients identification of the Ala38Thr polymorphism and suggested association between DRD3 haplotypes and schizophrenia. Mol Psychiatry 2000 5[4] 433—438. 

Inayama Y, Yoneda H, Sakai T, Ishida T, Nonomura Y, Kono Y et al. Positive association between a DNA sequence variant in the serotonin 2A receptor gene and schizophrenia. Am J Med Genet 1996 67[1] 103 105. 

Fluorine has been used to modulate the basicity of amines which may lead to an improvement in brain exposure. Recently, the discovery of a series of a4(32 nicotinic acetylcholine receptor (nAChR) potentiators as possible treatment for Parkinson s disease and schizophrenia was were disclosed [40]. Optimization of isoxazole 40 included the bioisosteric replacement of the central amide by an imidazole ring. Introduction of a fluorine at the 6-position of the phenyl ring provided compound 41. This compound had excellent potency but was determined to be a substrate for P-gp (efflux ratio >10). In an attempt to reduce amine basicity and decrease the efflux propensity, the 4-fluoropiperidine 42 was identified which retained potency and had significantly reduced P-gp efflux liability (efflux ratio 1). CNS penetration of 42 was observed in rodents following intraperitoneal (IP) treatment at 5mg/kg and showed a brain concentration of 6.5 gM. 

We still need much better medicines to cure cancer, heart disease, stroke, and Alzheimer s disease. We need better drugs to deal with obesity, diabetes, arthritis, and schizophrenia. The treatments of diabetes, arthritis, and mental defects such as schizophrenia or manic depression are not yet cures, just ways to keep the symptoms under control. Cures are needed. Insights from genetics may help guide us toward elegant and rational cures, but we will also make use of screens to identify natural products and libraries of randomly generated synthetic compounds (combinatorial chemistry). A semi-empirical approach may be the best hope over the next two decades to yield drugs to alleviate these diseases. 

Perturbation of the 5-HT system can elicit changes in a wide variety of behaviors. Furthermore, drugs that act on serotonergic neurons and their receptors are used to treat diseases such as depression, anxiety disorders and schizophrenia. Thus, 5-HT has been implicated in the regulation of many behaviors and physiological processes. The involvement of 5-HT in three areas - neuroendocrine function, circadian rhythms and feeding behavior - will be highlighted for illustrative purposes. 

Krystal, J. H., D Souza, D. C., Mathalon, D. et al. NMDA receptor antagonist effects, cortical glutamatergic function and schizophrenia toward a paradigm shift in medication development. Psychopharmacology 169 215-233, 2003. 

Kiriike,N., Izumiya,Y.,Nishiwaki, S. etal. TRH test and DST in schizoaffective mania, mania, and schizophrenia. Biol. Psych. 24 415-422,1988. 

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