Neurotransmitter analogue

There were several reasons for setting our sights on arylkainoid 254 as our first target. Firstly, being both highly active as a neurotransmitter analogue but also an unnatural product, it is a particularly desirable... 

Hydroxydopamine a neurotransmitter analogue that depletes noradrenergic stores in nerve endings and reduces dopamine levels in brain. Its mechanism of action is linked to cytolytic free-radical production. 

Joullie took advantage of the Kulinkovich-de Meijere reaction and synthesized a series of constrained A, A -dialkyl neurotransmitter analogues. For instance, indolylcyclopropylamine 50 was assembled from indole-olefm 49 and DMF in 52% yield. 

For a large number of dmgs, including neurotransmitters, peptide and protein hormones (qv), and thein analogues and antagonists, the ceU membrane is the principal locus of action. Concepts of ceU membrane stmcture are derived from the original Davson-DanieUi Hpid bilayer hypothesis. 

Methanol, l-isoquinolyl(phenyl)-confonnation, 2, 110 Methanol, pyrimidinyl-synthesis, 3, 113 Methanol, tetrahydropyran-2-yl-microwave spectra, 3, 625 Methantheline as neurotransmitter, 1, 175 therapeutic properties, 3, 882 Methaphenilene biological activity, 4, 911 Methapyrilene biological activity, 4, 911 toxicity, 4, 912 Methaqualone, 3, 150 as anticonvulsant, 1, 166 pyrido[2,3-d]pyrimidine analogues metabolism, 3, 205 as sedative, 1, 166 Metharbitone as anticonvulsant, 1, 166 Methazolamide... 

Pharmacology Acamprosate is a synthetic compound with a chemical structure similar to that of the endogenous amino acid homotaurine, which is a structural analogue of the amino acid neurotransmitter -aminobutyric acid and the amino acid neuromodulator taurine. 

Pregabaline is primarily an antiepileptic. Although it is an analogue of the neurotransmitter GABA it is not a GABA-agonist. It is mentioned here because it is also approved for use in generalized anxiety states. 

Baclofen (Lioresal) is the parachlorophenol analogue of the naturally occurring neurotransmitter y-aminobu-tyric acid (GABA). 

Dihydromuscimol (49) is a conformationally restricted analogue of the physiologically important neurotransmitter y-aminobutyric acid (GABA) and has been prepared using the cycloaddition of dibromoformaldoxime to A-Boc-allylamine followed by N-deprotection with sodium hydroxide (Scheme 6.52) (278). The individual enantiomers of dihydromuscimol were obtained by reaction of the bromonitrile oxide with (5)-( + )-l,2-0-isopropylidene-3-butene-l,2-diol, followed by separation of the diastereoisomeric mixture (erythro/threo 76 24), hydrolysis of respective isomers, and transformation of the glycol moiety into an amino group (279). 

HCA is the term is used to refer to both TCAs and analogues of these agents, such as maprotiline and amoxapine. TCAs are by far the most commonly used HCAs and include tertiary amines such as amitriptyline, doxepin, and imipramine and secondary amines such as desipramine and nortriptyline. Most secondary amines could also be viewed as NE-selective antidepressants, while the hallmark of tertiary amine TCAs is their effects on multiple neurotransmitters over their clinically relevant dosing range. 

There is evidence that in cerebral ischaemia adenosine may have protective effects, since it inhibits the release of many excitatory neurotransmitters, such as glutamate, and it also stabilises the membrane potential. Unfortunately, adenosine has an extremely short half-life, but recently nucleoside (adenosine) transport inhibitors, e.g. draflazine, have been developed that prevent the endothelial uptake and breakdown of adenosine and prolong its beneficial effects. Nucleoside transport inhibitors also have myocardial protective properties and may have a role in organ preservation prior to transplantation. Adenosine also has an antinociceptive function and various adenosine analogues have antinociceptive activity, which correlates with their affinity for the A1 receptors (Lipkowski and co-workers 1996). 

Phosphonates have been widely used as analogues of carboxylic acids. They have been particularly effective as analogues of tetrahedral transition states that occur in the course of enzyme-catalyzed reactions such as hydrolysis of the amide (peptide) bond. As such, they may be used as inhibitors of enzymes (e.g., 82, 83) or as haptens for producing antibodies that are catalytic (e.g., 84). A notable example is H203P— CH2—CH2—CH(—NH2)—COOH, which has effects that are likely to be due to its interference with glutamate as a neurotransmitter (85). 

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