Central nervous system antagonist effects

The benzodiazepine antagonist flumazenil is sometimes used to accelerate recovery from excessive sedative actions of intravenous benzodiazepines, but reversal of respiratory depression by flumazenil is less predictable. Its short duration of action (< 90 minutes) may necessitate multiple doses to prevent recurrence of central nervous system depressant effects of longer-acting benzodiazepines. 

All the clinically available (J-blockers are competitive antagonists. Nonselective [3-blockers act at both (3 and (32 receptors, whereas car-dioselective ( -antagonists primarily block 3i receptors. These drugs also differ in intrinsic sympathomimetic activity, in central nervous system (CNS) effects, and in pharmacokinetics (Figure 7.5). Although all (3-blockers lower blood pressure in hypertension, they do not induce postural hypotension because the a-adrenoceptors remain functional therefore, normal sympathetic control of the vasculature is maintained. P-blockers are also effective in treating angina, cardiac arrhythmias,... 

The most promising mechanism of action, which may account for some of caffeine s potential ergogenic effects, involves its demonstrated ability as a competitive antagonist of the depressant effects of adenosine analogs in the central nervous system. Adenosine and its derivatives have been shown to inhibit neuronal electrical activity, the release of neurotransmitters, and to interfere with synaptic transmission.19-24 27... 

The antidotal action of the barbiturates is probably limited to the effects of chlordan on the nervous system. They most likely have no beneficial antagonistic action against the delayed parenchymatous degenerative changes produced by chlordan (4). Therefore, they are primarily only of possible value in acute poisoning in which severe stimulation of the central nervous system may be the primary cause of death. 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

The precise mechanism of dimethylhydrazine toxicity is uncertain. In addition to the contact irritant effects, the acute effects of dimethylhydrazine exposure may involve the central nervous system as exemplified by tremors and convulsions (Shaffer and Wands 1973) and behavioral changes at sublethal doses (Streman et al. 1969). Back and Thomas (1963) noted that the deaths probably involve respiratory arrest and cardiovascular collapse. The central nervous system as a target is consistent with the delayed latency in response reported for dimethylhydrazine (Back and Thomas 1963). There is some evidence that 1,1-dimethylhydrazine may act as an inhibitor of glutamic acid decarboxylase, thereby adversely affecting the aminobutyric acid shunt, and could explain the latency of central-nervous-system effects (Back and Thomas 1963). Furthermore, vitamin B6 analogues that act as coenzymes in the aminobutyric acid shunt have been shown to be effective antagonists to 1,1-dimethylhydrazine toxicity (reviewed in Back and Thomas 1963). 

Memantine is approved for treatment of moderate to severe Alzheimer s disease. It is an antagonist at glutamatergic NMDA-receptors. Memantine is well tolerated and has a small beneficial effect at six months in moderate to severe AD (McShane et al. 2006). For patients with dementia one has to be careful wit all kind of medications that may affect the central nervous system. Delirium and hallucinations are common adverse effects in patients with dementia. Agitation may be due to delirium and external causes should be ruled out before adding another psychoactive drug. Sleep disturbance is common in demented elderly patients. Sleep deprivation may in a patient with dementia induce delirium. Nonpharmacological treatment for delirium or hallucinations should be considered first. 

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