Cognitive disorder

Aniracetam (6), launched in 1993 in both Japan and Italy for the treatment of cognition disorders, is in Phase II trials in the United States as of this writing. In clinical studies it has been shown to cause some improvement in elderly patients with mild to moderate mental deterioration (63), and in geriatric patients with cerebral insufficiency (64). In a multicenter double-blind placebo-controUed trial involving 109 patients with probable AD, positive effects were observed in 36% of patients after six months of treatment (65), a result repeated in a separate study of 115 patients (66). A review of the biological and pharmacokinetic properties, and clinical results of aniracetam treatment in cognitively impaired individuals is available (49). 

Use cognition disorders therapeutic, antagonist to narcotics, neuronal injury inhibitor... 

Letendre SL, McCutchan JA, Childers ME, Woods SP, Lazzaretto D, Heaton RK, Grant I, EUrs RJ (2004) Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol 56(3) 416 23... 

MasUah E, Heaton RK, Marcotte TD, EUis RJ, Wiley CA, MaUory M, Achim CL, McCutchan JA, Nelson JA, Atkinson JH, Grant I (1997) Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center. Ann Neurol 42(6) 963-972... 

The definitive identifieation of a therapeutie raison d etre for H3 antagonists will happen in the elinie. A handful of H3 ligands are reported to have entered elinieal testing. ABT-834 entered Phase-I trials for the indieation of cognitive disorders in May 2003 but no news has been reported since that time. GT-2331 (11) was approved for Phase-II clinical trials in 1999 but no news has been reported since then [4]. At this point, there are no data available to assess the therapeutic potential in human disease (See Table 5.1). 

The CBi binding affinity of the hydroxymethyl and carboxyl analogues can be increased by substituting the C3 pentyl side chain for a dimethylheptyl side chain (Table 6.13). 1 l-Hydroxy-l, l -DMH A -THC, HU-210 (165), is an extremely potent cannabinoid agonist that has been widely used as a pharmacological tool [119]. Its ( + ) enantiomer, HU-211 (dexanabinol), which is in clinical development for the treatment of cognitive disorders, does not have high affinity for CBi receptors [120]. 

Kristoikova Z and Klaschka J (1997). In vitro effect of Ginkgo biloba extract (EGb 761) on the activity of presynaptic cholinergic nerve terminals in rat hippocampus. Dementia <6 Geriatric Cognitive Disorders, 8, 43-48. 

Drugs that act on the H3 receptor are being developed for treating obesity, sleep disturbances, epilepsy and cognitive disorders 262... 

Drugs that act on the H3 receptor are being developed for the treatment of obesity, sleep disturbances, epilepsy and cognitive disorders. The ability of histamine to promote arousal, suppress appetite, elevate seizure threshold and stimulate cognitive processes implies that compounds able to enhance the release of neuronal histamine should mimic these effects. Several H3 antagonists currently in development demonstrate such activity and show promise as effective and novel therapeutic agents [40, 84-86]. Because H3 agonists suppress the release of... 

Drugs/Drug Classes Associated with Altered Cognition and/or Cognitive Disorders... 

Traditionally, most affective disorders have been treated with compounds that resemble the neurotransmitters that are deficient or in excess in specific brain regions. The aberrant levels of neurotransmitters (or their receptors), such as norepinephrine, dopamine, acetylcholine, and serotonin, have correlated with behavioral symptoms of schizophrenia, depression, anxiety, sleep disorders, motor dysfunctions, attention difficulties, and cognitive disorders. Most drugs discovered for these disorders resulted from screening compounds directly in rodent behavioral models that mimic the behavior of the disease. In these cases, the molecular target" or mechanism of action was assumed to be the deficiency or excess of a neurotransmitter. 

Perry EK, Perry RH, Smith G, Purohit D, Bonham 3, Dick DJ, Candy JM, Edwardson JA, Fairbairn A. (1986). Cholinergic receptors in cognitive disorders. Can J Neurol Sci. 13(4 suppi) 521-27. 

Howes M-JR, Perry NSL, Houghton PJ. (2003) Plants with traditional uses and activities, relevant to the management of Alzheimer s disease and other cognitive disorders. Phytother Res 17 1-18. 

Kaufer, D. (1998). Dementia and Geriatric Cognitive Disorders 9 (Suppl. 2), 8-14. 

The discovery that ACh was a transmitter in the peripheral nervous system formed the basis for the theory of neurotransmission. ACh is also a neurotransmitter in the mammalian brain however, only a few cholinergic tracts have been clearly delineated. ACh is an excitatory neurotransmitter in the mammalian CNS. There is good evidence that ACh (among other neurotransmitters) is decreased in certain cognitive disorders, such as Alzheimer s disease. 

FK-960 was initially developed for treatment of Alzheimer disease, but it has been abandoned for this indication. However, it is still under clinical trials for therapy of cognition disorders related to schizophrenia. 

Drugs that may cause cognitive disorders in the elderly. Med Let 2000 42 111-112. 

---