Schizophrenia

M J Marino, Worldwide Discovery Research, Cephalon, Inc., West Chester, PA, USA R E Davis, 3-D Pharmaceutical Consultants, San Diego, CA, USA H Meltzer, Psychiatric Hospital Vanderbilt, Nashville, TN, USA

L J S Knutsen and M Williams, Worldwide Discovery Research, Cephalon, Inc., West Chester, PA, USA

© 2007 Published by Elsevier Ltd.

6.02.1 Introduction 18

6.02.2 Disease State/Diagnosis 18

6.02.3 Disease Basis 19

6.02.3.1 The Dopamine (DA) Hypothesis 20

6.02.3.2 The Serotonin (5HT) Hypothesis 20

6.02.3.3 The Glutamate Hypofunction Hypothesis 20

6.02.3.4 The g-Amino-Butyric Acid (GABA) Hypothesis 21

6.02.3.5 The Clozapine Hypothesis 22

6.02.3.6 Genetic Insights 22

6.02.3.6.1 Catechol O-methyltransferase 23

6.02.3.6.2 Neuregulin 23

6.02.3.6.3 Dysbindin-1 23

6.02.3.6.4 Regulator of G protein signaling 4 23

6.02.3.6.6 Glutamate receptors 24

6.02.3.6.7 Disrupted-in-Schizophrenia 1 (DISC1) 24

6.02.3.6.8 CHRNA7 24

6.02.3.6.9 Miscellaneous associations 24

6.02.4 Experimental Disease Models 24

6.02.4.1 Behavioral Assays 25

6.02.4.1.1 Conditioned avoidance 25

6.02.4.1.2 Locomotor activity 25

6.02.4.1.3 Latent inhibition 25

6.02.4.1.4 Prepulse inhibition 26

6.02.4.2 Pharmacological Models 26

6.02.4.3 Lesion Models 27

6.02.4.4 Social Isolation Model 27

6.02.4.5 Genetic Models 28

6.02.5 Clinical Trial Issues 28

6.02.6 Current Treatment 29

6.02.6.1 First-Generation 'Typical' Antipsychotic Drugs 29

6.02.6.2 Second-Generation 'Atypical' Antipsychotic Drugs 32

6.02.6.3 Dopamine Receptor Modulators/Dopamine Partial Agonists 34

6.02.7 Unmet Medical Needs 35

6.02.7.1 Reduced Side Effect Liability 35

6.02.7.1.1 QTc liability 35

6.02.7.1.2 Metabolic syndrome 35

6.02.7.2 Broader Efficacy 36

6.02.8 New Research Areas 36

6.02.8.1 Muscarinic Agonists 36 6.02.8.1.1 N-Desmethyclozapine 37

6.02.8.2 Glutamate Modulators 37 6.02.8.2.1 N-Acetyl-L-aspartyl-L-glutamate 38

6.02.8.3 Neuronal Nicotinic Receptor Agonists 39

6.02.8.4 Neurokinin3 Antagonists 40 6.02.9 Future Directions 40 References 41

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

Get My Free Ebook


Post a comment