Angiotensin as a target for the treatment of Alzheimer's disease, anxiety and depression.
The brain renin-angiotensin system (RAS), which is comprised of a variety of peptides including angiotensin II, angiotensin III and angiotensin IV acting on AT<inf>1</inf>, AT<inf>2</inf> and AT<inf>4</inf> receptors, is important in cognition and anxiety. Perturbation of the RAS improves basal cognition and reverses age-, scopolamine-, ethanol- and diabetes-induced deficits. In studies of dementias and Alzheimer's disease (AD), some studies have shown that antihypertensive drugs, including angiotensin-converting enzyme inhibitors, have some moderate effects on cognitive decline, but that the angiotensin receptor antagonist losartan has a significantly beneficial effect. These findings suggest that angiotensin receptor ligands may have potential in the prevention or even reversal of vascular dementias and AD. With respect to depression and anxiety, there is similar experimental evidence from animal models that drugs acting on the RAS may be antidepressant or anxiolytic, but insufficient clinical data exist. Such effects, if proven, could promote the use of such agents in the treatment of hypertension coexisting with depression or anxiety.
University of Brighton, School of Pharmacy and Biomolecular Sciences, UK. p.r.gard@brighton.ac.uk
Paul R
PR
Gard
D000375:Aging / Q000523:psychology; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000517:prevention & control; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000809:Angiotensins / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000517:prevention & control; D001362:Avoidance Learning / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002491:Central Nervous System Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015897:Comorbidity; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000517:prevention & control; D019052:Depression, Postpartum / Q000188:drug therapy; D003866:Depressive Disorder / Q000188:drug therapy* / Q000517:prevention & control; D048909:Diabetes Complications / Q000188:drug therapy / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006801:Humans; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D000959:Antihypertensive Agents; D002491:Central Nervous System Agents; D018697:Nootropic Agents; D011945:Receptors, Angiotensin; D019808:Losartan