Antiprotozoals antimalarials

Q lllllflCrillC [Atebrine, 3-chloro-9(4-diethylamino-l-methyl)butylamino-7-methoxy)acridine] dihydrochloride. [69-05-6] M 472.9, m 248-250 (dec), pK -6.49 (aq H2SO4), pKj 7.73 (ring NH ), pKj 10.18 (Et2N). Cryst from H2O (sol 2.8% at room temp) as yellow crystals. Slightly sol in MeOH and EtOH. Antimalarial, antiprotozoal and intercalates DNA. [Wolfe Antibiot 3 (Springer-Verlag) 203 1975.]... 

Histones of Plasmodium falciparum represent a new target for antimalarials. Apicidin [Cyclo (N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2-amino-oxodecanoyl] is a potent, broad spectrum antiprotozoal agent. The target of apicidin is Histone deacetylases HDA (Darkin Rattray et al., 1996), evidenced as hyperacetylation of histones in treated parasites. 

Mayer, A. M. S., Rodriguez, A. D., Berlinck, R. G. S., and Hamann, M. T. (2009). Marine pharmacology in 2005-6 Marine compounds with anthelmintic, antibacterial, anticoagulant, antifungal, antiinflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities affecting the cardiovascular, immune and nervous systems, and other miscellaneous mechanisms of action. Biochim. Biophys. Acta 5, 283-308. 

Of interest is a recently described yeast-based, nutrient-dependent viability screen for inhibitors of protozoal dihydrofolate reductase (DHFR) [43,44], Antiprotozoal activity of DHFR inhibitors is well known, and DHFR- yeast complemented with the DHFR gene derived from the malaria parasite P. falciparum have been used to characterize the molecular pharmacology of resistance to the antimalarial DHFR inhibitors pyrimethamine and cycloguanil [45,46], The subsequent development of a screen was based on the demonstration that the protozoal... 

VENLAFAXINE 1. ANTIARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS — macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS-TCAs 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES-terfenadine, hydroxyzine, mizolastine 8. ANTIMALARIALS -artemetherwith lumefantrine, chloro-quine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS -pentamidine isetionate 10. ANTIPSY-CHOTICS - atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS -sotalol 12. BRONCHODILATORS-parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs cause prolongation of the Q-T interval Avoid co-administration... 

ANTIMALARIALS-artemetherwith lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 8. ANTIPROTOZOALS-pentamidine isetionate... 

Note that antimalarials are also antiprotozoals but have been described in a... 

ANTIMALARIALS - artemether with lume-fantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS -pentamidine isetionate 10. ANTI-PSYCHOTICS - atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS-parenteral bronchodilators 13. CNS STIMULANTS -atomoxetine... 

This section consists of antiprotozoal drugs. Note that antimalarials are also antiprotozoals but have been described in a separate section Antibiotics with antiprotozoal activity are not included in this chapter. These include clindamycin, co-trimoxazole/trimethoprim, dapsone, doxycydine and metronidazole ... 

Pyrimethamine is the most active antimalarial of the 2-4-diaminopyrimidines, its effect being due to inhibition of the conversion of foUc acid to its active form, folinic acid. It is also effective in toxoplasmosis. Its antiprotozoal and antimalarial activity is enhanced by the addition of sulfonamides. 

Pyrimethamine and proguanil are used as oral antimalarials.and inhibit the utilization of folate by the malarial parasite, so are valuable in chemoprophylaxis and in preventing the transmission of malaria. (See ANTIMALARIALS.) Trimethoprim is a useful antibacterial, and as an antiprotozoal in antimalarial therapy. The selectivity of these agents derives, in part, from the fact that whereas mammals can obtain folic acid from the diet, bacteria and the asexual forms of the malarial parasite must synthesize it. Also, the dihydrofolate reductase enzyme in humans is less sensitive to these drugs than that of the parasites. 

Menzol norethisterone. mepacrine [ban, inn] (quinacrine hydrochloride [usan]) can be used as an antimalarial and ANTHELMINTIC. It also acts as a POTASSIUM-CHANNEL BLOCKER (IsKICal)-mepartricin [ban, inn, usan] (Mepartricin A) is a (polyene group) ANTIBIOTIC mixture with ANTIFUNGAL and ANTIPROTOZOAL activity. Clinically, it can be used topically, principally for candidiasis. 

The non-classical antimetabolite approach, on the other hand, appears to have struck gold recently in the field of antimalarials as well as other antiprotozoal and antibacterial agents. If the reported animal screening results are any indication of the therapeutic usefulness of the new 2,4-diaminoquinazolines and related compounds, then one would think that the goal of eradicating these parasitic diseases is in sight. 

Trade names Malarone (GSK) Mepron (GSK) Wellvone Indications Pneumocystis carinii infection Category Antimalarial Antiprotozoal Half-life 2.2-2 9 days... 

Indications Malaria, rheumatoid arthritis, lupus erythematosus Category Antimalarial Antiprotozoal Disease-modifying antirheumatic Half-life 3-5 days... 

Trade names Cardine Cin-Quin Gluquine Kinidin Quinalan Quinate Quini Durules Quinora Indications Tachycardia, atrial fibrillation Category Antiarrhythmic class la Antimalarial Antiprotozoal Half-life 6-8 hours... 

Trade names Adaquin Chinine Formula-Q Genin M-KYA Q-Vel Quinoctal Quinsan Quinsul Quiphile Indications Malaria, nocturnal leg cramps Category Antimalarial Antiprotozoal Half-life 8-14 hours... 

Among the various natural products, which have been found to possess antiprotozoal activity in humans, quinine (2) and qinghaosu (7) have undergone extensive molecular modifications to obtain better antimalarial drugs. The salient results of these studies are described below. 

Campnosperma panamense Standi, (leaves) Lanaroflavone (249). Antiprotozoal activity. antimalarial and leishmanicidal activities, but inactive against Chagas disease vector. Trypanosoma cruzi. Weniger et al., 2001 [126], 2004 [70], 2006[86]. 

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