Potent significance

A major concern when remediating wood-treatment sites is that pentachlorophenol was often used in combination with metal salts, and these compounds, such as chromated copper—arsenate, are potent inhibitors of at least some pentachlorophenol degrading organisms (49). Sites with significant levels of such inorganics may not be suitable candidates for bioremediation. 

Codeine, mol wt 299.3, is a significantly less potent analgesic than morphine, requiring 60 mg (0.20 mmol) to equal the effectiveness of 10 mg (0.04 mmol) of morphine. However, codeine is orally effective, and it is less addictive and associated with less nausea than morphine. Codeine is used as an antitussive agent, although newer, nonaddictive agents are preferred (see Expectorants, antitussives, and related agents). 

Desflurane is less potent than the other fluorinated anesthetics having MAC values of 5.7 to 8.9% in animals (76,85), and 6% to 7.25% in surgical patients. The respiratory effects are similar to isoflurane. Heart rate is somewhat increased and blood pressure decreased with increasing concentrations. Cardiac output remains fairly stable. Desflurane does not sensitize the myocardium to epinephrine relative to isoflurane (86). EEG effects are similar to isoflurane and muscle relaxation is satisfactory (87). Desflurane is not metabolized to any significant extent (88,89) as levels of fluoride ion in the semm and urine are not increased even after prolonged exposure. Desflurane appears to offer advantages over sevoflurane and other inhaled anesthetics because of its limited solubiHty in blood and other tissues. It is the least metabolized of current agents. 

Initially, it was beheved that the abiUty of xanthines phosphodiesterase (PDF) led to bronchodilation (Fig. 2). One significant flaw in this proposal is that the concentration of theophylline needed to significantly inhibit PDE in vitro is higher than the therapeutically useful semm values (72). It is possible that concentration of theophylline in airways smooth muscle occurs, but there is no support for this idea from tissue distribution studies. Furthermore, other potent PDE inhibitors such as dipyridamole [58-32-2] are not bronchodilators (73). EinaHy, although clinical studies have shown that neither po nor continuous iv theophylline has a direct effect on circulating cycHc AMP levels (74,75), one study has shown that iv theophylline significant potentiates the increase in cycHc AMP levels induced by isoproterenol (74). 

Ivermectin is the catalytic reduction product of avermectin, a macroHde containing a spiroketal ring system. Two other related antibiotics having significantly different stmctural features and biological properties, moxidectin and milbemycin oxime, were more recentiy introduced into the market. Although these compounds have no antimicrobial activity, they are sometimes referred to as antibiotics because they are derived from fermentation products and have very selective toxicities. They have potent activity against worms or helminths and certain ectoparasites such as mites and ticks. 

The biosynthesis of the fortimicins has received some initial study (220—222) and a significant amount of semisynthetic modification has been carried out in this series. 3-0-Demethylfortimicin A (223,224) was found to be significantly more potent than the parent fortmicin A, especially against P aeruginosa 3-0-Demethyl-2-epi-, 2,3-di-epi-, and 3-0-demethyl-2,3-di-epi-fortimicin A are somewhat less active than fortimicin A, but the... 

The sulfated compounds MM 13902 (3, n = (5) and MM 17880 (4) are also broad-spectmm agents, but not as potent as thienamycia and all lack any significant activity against Pseudomonas (73). Many carbapenems are excellent inhibitors of isolated P-lactamases, particularly the olivanic acid sulfoxide MM 4550 (3, n = 1) (3). The possible mechanism of action of the carbapenems as inhibitors of P-lactamases has been discussed in some detail (74). Other carbapenems such as PS-5 (5) (75), the carpetimycins (76), asparenomycins (77), and pluracidomycins (8) are all highly active as antibiotics or P-lactamase inhibitors. The parent nucleus itself (1, X = CH2) is intrinsically active, but chemically unstable (9). 

Another dideoxypyrimidine nucleoside active against human immunodeficiency vims is 3 -azido-2/3 -dideoxyuridine [84472-85-5] (AZDU or CS-87, 64) C H N O. Since its synthesis, (167) CS-87 has been identified as a promising antiHIV agent (168) and is currentiy undergoing phase I clinical trials in patients with AIDS and AIDS-related complex. It appears to be less potent than AZT against HIV in a peripheral blood mononuclear (PBM) cell screening system and in MT-4 cell lines. This lower activity in PBM cells appears to be related to a lower affinity of CS-87 for the enzyme responsible for its initial phosphorylation (169). However, CS-87 has significantly lower toxicity on bone marrow cells than AZT (170) and penetration of the CNS as a 5 -dihydropyridine derivative. 

Nicorandil. Nicorandil is a potassium channel opener that can lower blood pressure 21, 20, and 29 mm Hg after single oral doses of 10, 20, and 30 mg, respectively (250). There are no significant changes ia heart rate. Headache is the primary side effect. Nicorandil has potent coronary vasodilator effects. It causes sustained vasodilation of arteriolar resistance and venous capacitance blood vessels, thus reduciag cardiac preload and aftedoad. 

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