Pharmacological modulation of circadian rhythms: a new drug target in psychotherapeutics.
Daily variation in an organism's physiology and behaviour is regulated by the synchrony that is achieved between the internal timing mechanisms - the circadian rhythms of the biological clock - and the prevailing environmental cues. Proper synchrony constitutes an adaptive response; improper or lost synchrony may well yield maladaptation and, in the case of humans, a psychiatric disorder. On a basic level, the circadian system is comprised of three parts: a central oscillator, its various neuronal inputs and its outputs. For all three of these parts, the dissemination of new information is moving at an unprecedented pace, and the number of molecular targets for the opportunistic pharmacologist is growing in step. Monoamines, neuropeptides, kinases - sorting through all these, much less developing one into a drug discovery programme, may be the biggest challenge. However, the potential benefits in targeting a basic flaw in a fundamental biological system may be enormous.
Pfizer Global Research & Development, Groton, CT 06340, USA. sprousejs@groton.pfizer.com
Jeffrey
J
Sprouse
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001127:Arginine Vasopressin / Q000502:physiology; D048149:Casein Kinase 1 epsilon / Q000502:physiology; D048148:Casein Kinase Idelta / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects* / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008027:Light; D008550:Melatonin / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D019964:Mood Disorders / Q000188:drug therapy* / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000187:drug effects / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D020919:Sleep Disorders, Intrinsic / Q000188:drug therapy / Q000503:physiopathology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology
D000928:Antidepressive Agents; D009479:Neuropeptides; D011619:Psychotropic Drugs; D011985:Receptors, Serotonin; D001127:Arginine Vasopressin; D012701:Serotonin; D048149:Casein Kinase 1 epsilon; D048148:Casein Kinase Idelta; D008550:Melatonin