8-blockers antagonists

FDA approved alcohol and opioid treatment. Also being tested as a cocaine treatment Receptor blockers (antagonist)... 

In Chapter 1 we discussed how modern psychopharmacology is essentially the study of chemical neurotransmission. In this chapter we will become more specific and discuss how virtually all central nervous system (CNS) drugs act in one of two very specific ways on chemical neurotransmission first and most prominently as stimulators (agonists) or blockers (antagonists) of neurotransmitter receptors or second, and less commonly, as inhibitors of regulatory enzymes. 

Therefore, the utility of this cycloaddition in total synthesis was highlighted by Leighton and co-workers during their asymmetric synthesis of (+)-manzacidin C 70 via a chiral silane-promoted diastereoselective and enantiose-lective acyUiydrazone-alkene [3+2] cycloaddition reaction (Scheme 41.14). The manzacidins were isolated from the Okinawan sponge Hymeniacidon, and they possess activities such as a-adrenoceptor blockers, antagonists of serotonergic receptors, and actomyosin adenosine... 

Prolonged exposure of -adrenoceptor agonists down-regulates -adrenoceptors, ie, their number decreases and they become less responsive. On the other hand, prolonged exposure to -adrenoceptor antagonists (those without ISA) upregulates -adrenoceptors, ie, their numbers increase and they become more responsive. Therefore, patients on -adrenoceptor blocker therapy should be withdrawn from this medication gradually (40). 

The cardiac effects of the calcium antagonists, ie, slowed rate (negative chronotropy) and decreased contractile force (negative inotropy), are prominent in isolated cardiac preparations. However, in the intact circulation, these effects may be masked by reflex compensatory adjustments to the hypotension that these agents produce. The negative inotropic activity of the calcium antagonists may be a problem in patients having heart failure, where contractility is already depressed, or in patients on concomitant -adrenoceptor blockers where reflex compensatory mechanisms are reduced. 

The use of selective P-antagonists for treatment of CHF has included the P -blocker metoprolol (Table 1) and results of clinical trials suggest long-term beneficial effects. Selective P -antagonists have also been tested, an example of which is xamoterol [81801 -12-9], C2 H25N20, which is (i)-A/-(2-hydroxy-3-(4-hydroxyphenoxy)propylamino)ethylmorphine-4-carboxamide. Xamoterol exhibits approximately 50% of the activity of isoproterenol, and serves to provide modest inotropic effects (128,129). 

The synthetic utihty of the above transformations stems from the fact that many monoesters obtained as a result of hydrolysis may be converted to pharmaceutically important intermediates. For example, the optically active glycerol derivative (27) is a key intermediate in the production of P-blockers. Akyl derivative (25) may be converted into (5)-paraconic acid [4694-66-0] ((5)-5-oxo-3-tetrahydrofurancarboxyhc acid) that is a starting material for the synthesis of (3R)-A-factor. The unsaturated chiral cycHc monoacetate (31) is an optically active synthon for prostaglandins, and the monoester (29) is used for the synthesis of platelet activating factor (PAF) antagonists. 

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... 

Compounds which act as antagonists at the receptors for beta sympathetic transmitters (beta blockers) have gained very wide acceptance as antihypertensive agents. It was found subsequent to their introduction that there are two populations of beta receptors the beta-1 receptors are richest in the cardiovascular system whereas beta-2 receptors are mostly found in the bronchi. Lack of receptor-type specificity led to bronchial spasm in some asthmatic individuals on ingestion of the earlier beta blockers. Much of the work outlined below had as its goal the preparation of agents which showed selectivity for beta-1 receptors. 

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