Neurotransmitter antagonist

Some recent reports on this type of neurotransmitter antagonists are available [199-204]. 

Stereoselective synthesis of optically active ff-amino alcohols is highly desirable, because such units are seen ubiquitously in the structures of many biologically active compounds represented by neurotransmitter antagonists, antimicrobials, and pain killers. Hydroboration of the a-bromo ketone 51 promoted by the amino alcohol 54 gives a key intermediate 52 for the synthesis of the (i ,/ )-isomer of Formoterol (53), a long acting )52-agonist used in the treatment of asthma (Scheme 15) [52]. 

PCP has widely varied actions including CNS stimulation, depression, and hallucinogenic properties. Pharmacologically, it is known to block reuptake of serotonin, dopamine, and norepinephrine, but neurotransmitter antagonists do not effectively block its effects. In low doses, PCP causes sedation, ataxia, nystagmus, slurred speech, and paresthesias. At higher doses, users experience an increase in heart rate, blood pressure, temperature, diaphoresis, and muscle rigidity. At acutely toxic doses, coma and seizures may occur." ... 

Non-planar sulfur or phosphorous-derived acidic functions The most extensive use of phosphonates was made in the design of amino acid neurotransmitter antagonists such as glutamate and GABAb antagonists. ... 

A polyamino carbonyl ferrocene dmivative formed by coupling ferrocene carboxylic acid with a BOC protected polyamine is claimed to be a mammalian excitatory neurotransmitter antagonist. Ferrocenyltetrazolylhydrozones have been prqrared from the condensation reaction of ferrocenecarboxaldehyde with a series of tetrazolylhydrazines. The reaction of ferrocoie carboxaldehyde with CH2(COR)(COR ), R = Me, R = Me, OEt in ether containing a Lewis base results in the formation of FcCH=C(COR)COR (mixture of E and Z isomers the work is extendable to diferrocenyl derivatives. Further work on the reduction of fluorine substituted methyl acetylferrocenes has been reported. "... 

One of the fundamental features of aprepitant, and a major advantage it has over other chemotherapy-induced side-effect treatments, is that while it successfully antagonises the NKl receptors it has very little affinity over other receptors such as serotonin, dopamine, and corticosteroids. It is estimated that aprepitant is at least 3000 times more selective of NKl receptors compared to the other well-known neurotransmitter antagonists. 

Histamine AND histamine antagonists). It is formed from histidine by the enzyme L-histidine decarboxylase. In the periphery, histamine is stored ia mast cells, basophils, cells of the gastric mucosa, and epidermal cells. In the CNS, histamine is released from nerve cells and acts as a neurotransmitter. The actions of histamine ate terrninated by methylation and subsequent oxidation via the enzymes histamine-/V-methyltransferase and monoamine oxidase. 

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. 

Prazosin, a selective a -adrenoceptor antagonist, exerts its antihypertensive effect by blocking the vasoconstrictor action of adrenergic neurotransmitter, norepinephrine, at a -adrenoceptors in the vasculature (200,227,228). Prazosin lowers blood pressure without producing a marked reflex tachycardia. It causes arteriolar and venular vasodilation, but a significant side effect is fluid retention. Prazosin increases HDL cholesterol, decreases LDL cholesterol, and does not cause glucose intolerance. 

The ergolines have provided a number of drugs that show interaction with neurotransmitters. Depending on the substitution pattern, they may be dopamine agonists or antagonists, a-adrenergic blockers, or Inhibitors of the release of prolactin. A recent member of the series, pergolide... 

Subtype, often refers to a receptor and denotes a variation in the gene product such that the endogenous ligand is the same (i.e., neurotransmitter, hormone) but the function, distribution, and sensitivity of the receptor subtypes differ. Antagonists often can distinguish receptor subtypes. 

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

A 17 amino acid long peptide sequentially related to opioid peptides in particular dynorphin A. OFQ/N is inactive at the 5, k, and p opioid receptors, but binds to its own NOP receptor (formerly ORL-1, for opioid receptor like-1). In contrast to opioid peptides, OFQ/N has no direct analgesic properties. OFQ/N is the first example for the discovery of a novel neurotransmitter from tissue extracts by using an orphan receptor as bait. Centrally administered in rodents, OFQ/N exerts anxiolytic properties. OFQ/N agonists and antagonists... 

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