Nootropics

The compounds used to palliate the mnemonic and cognitive decline associated with dementia include cerebral vasodilators and the so-called nootropic agents. These materials enhance cerebral metaboHsm. Agents which enhance neurotransmitter function are in most cases cholinergic. 

The term nootropic has been used to describe a class of compounds defined by the abibty of its members to facibtate learning (36). The compounds are most effective in animals that have had their cognitive abihties compromised in some way. The molecular mechanism undedying the cognitive-enhancing... 

The mechanism of action of nootropic agents has been proposed to be their abiUty to faciUtate information acquisition, consoHdation, and retrieval (36). No one particular effect has been observed with any consistency for these agents, thus whereas a considerable amount of diverse preclinical pharmacological behavioral data has been generated using these compounds, the significance of these results in predicting clinical efficacy has not been established (43,44). Reviews on the biochemical and behavioral effects of nootropics are available (45—47). 

Other nootropic agents in some stage of clinical development include nebracetam (9), nefinacetam (10), and BMY 21502 (11). Nebracetam, an aminomethyl pyrrolidinone derivative, is expected to be approved in Japan in 1994 (73). In clinical studies involving patients having cerebrovascular or senile dementia of the Alzheimer s type, clinical symptoms such as spontaneous or emotional expression were enhanced in up to 71% of cases. Long-term treatment using nebracetam in patients with cerebral infarction also afforded marked improvement in most cases with few side effects (74). A review of this compound has beenpubUshed (75). 

LTP) in hippocampal slices (89,90). LTP is believed to be a critical step in memory acquisition, and agents that possess the abiUty to augment this process in vivo are expected to be of benefit in memory enhancement. However, this compound has only demonstrated this property in vitro. In addition, because (11) does not appear to affect other neurotransmitter systems, as do other nootropics, the potential of BMY 21502 as a memory-enhancing agent is questionable. 

There appear to be a number of clinical studies that support the efficacy of various nootropic agents in patients with some form or degree of dementia, but the results are not particularly convincing (50,51,57—59,63,74). 

Chemistry, pharmacology, and clinical efficacy of the Chinese nootropic agent huperzine A, alkaloid from Hupenia sermta with annulated 2-pyridone and l-amino-3-methyl-9-ethylidenebicyclo[3.3.l]nona-2,6-diene fragments 99ACR641. 

CV-2619) Use senile dementia therapeutic, coenzyme QIO derivative, nootropic... 

In the face of the failure of rational approaches in the treatment of AzD it is perhaps not surprising that there have been many less rational ones. These include the use of vasodilators and nootropics. The former, such as hydergine, a mixture of ergot alkaloids, are intended to increase cerebral blood flow and neuronal metabolism despite some reduction in blood pressure, while the latter, like piracetam, are metabolic stimulants that increase cerebral metabolism and ATP production. Neither are of proven value in AzD. 

Nootropics Slow cognitive decline in dementia Aricept, tacrine... 

Table 14.1. Nootropics the proposed modes of actions for several putative cognitive enhancers. 

Hydergine A mixture of the three dihydro-derivatives of the alkaloids in ergotoxine. It is used as a cerebral vasodilator and reported to have nootropic effects. 

---