Cognition-activating properties of 3-(aryloxy)pyridines

Butler, Donald E.; Poschel, B. P. H.; Marriott, John G.

doi:10.1021/jm00135a020

Cited by 50 publications

(12 citation statements)

References 3 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19821. Thus the present neurochemical finding indicating a hellshaped dose-response curve or therapeutic window effect of pramiracetam should not be considered unusual, as it has also been observed in behavioral studies with other cognitive activator agents [Bartus, 1979: Butler et al, 1981Cumin et al, 19821. The mechanism underlying the stimulation of in vitro HACU after in vivo pramiracetam administration is open to speculation. Direct addition of pramiracetam and other test agents to samples from control hippocampal preparations did not alter uptake.…”

Section: Discussionsupporting

confidence: 66%

Some neurochemical properties of pramiracetam (CI‐879), a new cognition‐enhancing agent

Pugsley

Shih

Coughenour

et al. 1983

Drug Development Research

View full text Add to dashboard Cite

The present study was initiated to examine the effect of pramiracetam sulfate [N-[B[bis(lrnethylethyl)amino]ethyl]-2 oxo-l-pyrrolidineacetamide sulfate (1 :1)] (PR), a new cognitionactivator agent, on various neurochemical parameters in order to gain some insight into the mechanism of action of this agent. PR (100 mg/kg i.p.) did not alter the concentration of norepinephrine, dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic, and homovanillic acid in various brain areas. The agent also did not alter d-methamphetamine-induced changes in monoarnine metabolism nor prolactin concentration in rat serum. PR did not exhibit any affinity in vitro for doparninergic, adrenergic, serotoninergic, GABAergic, muscarinic, adenosine (ICs0 > 10 pM), and benzodiazepine receptors (ICs0 > 1 pM) binding sites. It may be concluded that the mechanism of action of pramiracetam does not appear to be due to a direct action upon DA and 5-HT neurotransmitter systems or various brain receptors. PR (44 and 88 mglkg i.p.) caused a significant increase in the rate of sodiumdependent high-affinity choline uptake (HACU) into rat hippocampal synptosomes in vitro. This was specific as no effect was observed in cerebral cortex and corpus striaturn. These results would seem to indicate that PR is accelerating hippocampal acetylcholine turnover and thus septal-hippocampal cholinergic neuronal impulse flow. This effect could be at least partially responsible for the enhancement of cognition processes observed for this agent.

show abstract

Section: Discussionsupporting

confidence: 66%

Some neurochemical properties of pramiracetam (CI‐879), a new cognition‐enhancing agent

Pugsley

Shih

Coughenour

et al. 1983

Drug Development Research

View full text Add to dashboard Cite

show abstract

“…On the basis of considerations of the electronic effects of the sulfamoyl and carbonyl groups, it may be shown that the difference in chemical shift of the aromatic protons in la should be larger than that of 2a. Indeed, (5)(6)(7)(8) was found to be 0.48 and 0.29 ppm, respectively. The S02NH2 and [CONH «=t C(OH)=N] signals appear as sharp singlets in the spectrum of 2a, whereas for la no NH peak can be observed in the 9-14-ppm region and the S02NH2 appears as a very broad peak (see Figure 3).…”

Section: T H Imentioning

confidence: 96%

“…Method A. The key intermediate 4-chloro-5sulfamoylphthalimide 17,6 obtained by the reaction of 2,4-dichlorosulfamoylbenzoic acid (16) with cuprous cyanide in DMF,7 was reduced by Zn/acetic acid to the corresponding 3-hydroxyphthalimidine 18. Condensation of the latter with hydrazines afforded the phthalazinones la-e.…”

Section: Chemistrymentioning

confidence: 99%

“…3.68 (s, 3 H, CH3), 6.8 (s, 2 H, NH2), 7.34 (s, 1 H, C5-H), 8.3 (s, 1 H, C8-H), 8.45 (s, 1 H, C4-H) 5.3 (s, 2 H, CH2), 6.0-6.9 (m, 2 H, NH2), 7.35 (a, 5 H, Ph), 7.1 (s, 1 H, C5-H), 8.1 (a, 1 H, C8-H), 8.27 (s, 1 H, C4-H) 6.72 (br s, 2 , NH2), 7.12, 7.8, 8.0, 8.1, 8.4 (7 H, TFMPh, C"-H, C5-H, C4-H) 2.95 (s, 9 H, 3 CH3), 3.21 (s, 3 H, CH3), 5.87 (m, 1 H, C3-H), 7.0 (m, 1 H, OH), 7.77 (s, 1 H, C4-H), 8.0 (s, 1 H, Me2NCH=N), 8.17 (a, 1 H, C7-H), 8.36 (s, 1 H, Me2NCH=NS02) 5.85 (br s, 2 H, NH2), 7.35 (br s, 4 H, formula C15H12N4OF3CF TFMPh), 3.5 (a, 2 H, C6-H, benzal), 8.5 (s, 1 H, C3-H), 10.9 (s, 1 , NNH) "For general experimental data, see Experimental Section. 6 Yields were in no case optimized.…”

Section: T H Imentioning

confidence: 99%

“…All compounds were subjected to a preliminary screening for diuretic, saluretic, and antihypertensive activity in the 6 Beats/minute + SEM. c p < 0.05. d0.05 <p< 0.10. rat, and the results are summarized in Tables III-V.…”

Section: Pharmacologymentioning

confidence: 99%

See 2 more Smart Citations

Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones

Cherkez¹,

Herzig²,

Yellin³

1986

J. Med. Chem.

View full text Add to dashboard Cite

The synthesis of the isomeric series 6-chloro-7-sulfamoyl- and 7-chloro-6-sulfamoyl-1(2H)-phthalazinones (1 and 2) and 6-chloro-7-sulfamoyl- and 7-chloro-6-sulfamoyl-3,4-dihydo-1(2H)-phthalazinones (3 and 4), combining structural features characteristic to furosemide and hydralazine, is described, the mechanism of the formation of 1 and 2 is discussed, and their structure-activities relationships are studied. Preliminary screening in the rat shows that series 1 and 3 exhibit diuretic and saluretic activity similar to that of chlorothiazide with, however, Na+/K+ ratios more favorable than chlorothiazide and furosemide. The compounds of series 2 and 4 are practically inactive. All four series show initial antihypertensive activity lower than that of hydralazine. However, compounds 1a, 1c, and 4a show a higher activity at 8 and/or 24 h after administration and thus may offer a unique combination of a "loop" diuresis with direct long-acting peripheral vasodilating effects.

show abstract

Cognition

Young¹

2021

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

Cognition can be defined as neurocognitive processes of how humans learn and remember. As humans age, threats of neurocognitive disturbances are probably the most feared psychiatric problems, but these processes also can be disrupted by biological abnormalities closely connected to other psychiatric problems. The theme of this article is that basic research in areas of cognition and advances in the discovery of novel pharmacotherapy for neurocognitive and psychiatric disorders that affect the elderly are inextricably intertwined. Drug evaluations in animal models should be conducted in, three basic types of learning/memory paradigms (habituation, classical conditioning, and operant conditioning) and should assess the effects of agent on learning, retention, and retrieval. The importance of this strategy involves issues of single or multiple learning processes in the paradigms, whether different types of paradigms give rise to different kinds of memories or whether the same paradigm may produce several fundamentally different types of memories that may or may not be interdependent. Medications currently in use for ameliorating neurocognitive disorders are mostly ineffective. New pharmacotherapy is urgently needed, and a seemingly innumerable collection of drugs has been proposed as the latest “key” to unlock mechanisms of dysfunction in neurocognition. In some cases, new agents have functioned (biochemically) exactly as advertised, but virtually all have proved unacceptable for clinically use. Future therapies for neurocognitive disorders will likely benefit from the recognition that multiple cellular mechanisms and neurotransmitter processes are involved and that administration of combinations of agents that provide “wide‐spectrum” actions may be most useful.

show abstract

Cognition-activating properties of 3-(aryloxy)pyridines

Cited by 50 publications

References 3 publications

Some neurochemical properties of pramiracetam (CI‐879), a new cognition‐enhancing agent

Some neurochemical properties of pramiracetam (CI‐879), a new cognition‐enhancing agent

Synthesis, saludiuretic, and antihypertensive activity of 6,7-disubstituted 1(2H)- and 3,4-dihydro-1(2H)-phthalazinones

Cognition

Contact Info

Product

Resources

About