Disease relevance of quinacrine

• Correlation of clinical findings with quinacrine-banded chromosomes in 90 adults with acute nonlymphocytic leukemia: an eight-year study (1970-1977) [1].
• Quinacrine ochronosis [2].
• (b) Combined quinacrine and metronidazole, which cured our patient's chronic giardiasis, should be tried in patients in whom infection persists after single drug therapy [3].
• The quinacrine method of non-surgical female sterilisation involves transcervical intrauterine insertion of 252 mg quinacrine as pellets during the proliferative phase of the menstrual cycle; the drug causes inflammation and fibrosis of the proximal fallopian tube [4].
• There was one birth defect (anencephaly), in a fetus conceived 2.5 months after quinacrine insertions; however, we believe it is not related to the procedure [4].

Psychiatry related information on quinacrine

• Because quinacrine and chlorpromazine have been used in humans for many years as antimalarial and antipsychotic drugs, respectively, and are known to pass the blood-brain barrier, we suggest that they are immediate candidates for the treatment of Creutzfeldt-Jakob disease and other prion diseases [5].
• Furthermore, neither LHRH-induced LH release from preprimed tissue nor Ca(2+)-induced LH release were attenuated by quinacrine, indicating that this inhibitor does not interfere with the general Ca(2+)-dependent secretory apparatus of the gonadotroph and that the critical period for its action is in the induction of priming [6].
• Recovery of the hypoxia-exposed mice to a normal rhythm in T(b), motor activity and feeding was unaffected by mepacrine, a phospholipase A(2) blocker [7].

High impact information on quinacrine

• We find that the IM-augmenting effects of somatostatin are abolished by two substances that can inhibit phospholipase A2, quinacrine and 4-bromophenacyl bromide, and that both arachidonic acid and leukotriene C4 mimic the effects of somatostatin-14 on hippocampal pyramidal neurons in vitro [8].
• Y chromosome visibility in quinacrine-stained human spermatozoa [9].
• Quinacrine ochronosis and rheumatoid arthritis [10].
• Pyrrolidine dithiocarbamate, an inhibitor of oxidative NF-kappaB activation, diphenylene iodonium, an NADPH oxidase inhibitor, and quinacrine, a phospholipase A2 inhibitor, significantly attenuated the increase in dichlorofluorescein fluorescence, NF-kappaB activation, and NO production [11].
• When 10(-9) M ET-1 was added in the presence of 10(-5) M quinacrine, a phospholipase (PL) inhibitor, Jv also increased from 1.02 +/- 0.20 to 1.23 +/- 0.22 nl/mm/min (P < 0.03) [12].

Chemical compound and disease context of quinacrine

• Medical methods include instillation of antineoplastic agents, antimicrobial agents, or colloidal radioisotopes into the pleural space; quinacrine and tetracycline are moderately to highly effective agents, but the toxicity of the former is substantial [13].
• We report that quinacrine, chloroquine, and structurally related compounds completely inhibit the antiapoptotic effect of CpG-ODN on WEHI 231 murine B lymphoma cells and inhibit CpG-ODN-induced secretion of IL-6 by WEHI 231 [14].
• Activation of wild-type as well as F347A, D100N or K333M/K334T/R335L CCK2 receptors by this ligand led to a similar arachidonic acid release which was blocked by pertussis toxin and the phospholipase A2 inhibitor, mepacrine [15].
• METHODS--Forty patients with carcinoma and pleural effusions refractory to repeated pleural aspirations over the previous 12 weeks were randomised to receive treatment with intrathoracic instillation of mepacrine or bleomycin [16].
• Activity of picolinic acid in combination with the antiprotozoal drug quinacrine against Mycobacterium avium complex [17].

Biological context of quinacrine

• Quinacrine fluorescence analysis revealed that cells with No. 2 trisomy or either of two types of long No. 2 had total and partial No. 2 trisomy, respectively [18].
• Prostaglandin E2 (10(-5) M), indomethacin (10(-6) M), piroxicam (5 x 10(-5) M), and mepacrine (10(-4) M) partially inhibited the amebic lysate effect on active transport in the rat descending colon [19].
• The exocytosis of intact dense bodies can be observed either by DIC microscopy, or by epifluorescence microscopy in platelets stained with mepacrine [20].
• The combination of 3-deazaadenosine and homocysteine thiolactone, which inhibits phospholipid methylation, and quinacrine, an inhibitor of phospholipase A2, also abolishes the response to the peptide [21].
• The binding site for quinacrine in the open channel of mouse-muscle ACh receptor was mapped in cysteine-substituted mutants of the alpha subunit expressed with wild-type beta, gamma, and delta subunits [22].

Anatomical context of quinacrine

• The compound ATP gamma S inhibits agonist-stimulated adenylate cyclase activity in solubilized and in isobutylmethylxanthine (IBMX) and quinacrine pretreated membranes, suggesting that ATP gamma S inhibition occurs independent of AVP and A1 adenosine receptors and of phospholipase A2 activity [23].
• BK also stimulates the synthesis of PGE2 in rabbit ileal and colonic mucosa and this effect can be blocked by prior addition of either indomethacin or mepacrine [24].
• Treatment with SC41930 significantly reduced, whereas either WEB2086 or quinacrine completely abolished, the increased leukocyte adherence and emigration induced by L-NAME [25].
• Labeling the vacuole with either quinacrine or FITC-dextran revealed vacuole fragmentation that was not found in untreated cells or in cells arrested in G2 by unrelated means [26].
• In support of this hypothesis, the distribution of methylaminoisobutyrate between plasma membrane vesicles and their supporting media was influenced in the predictable way by NADH, quinacrine, and an uncoupling agent, proceeding on the assumption that more of the vesicles had the everted rather than the natural orientation [27].

Associations of quinacrine with other chemical compounds

• In vitro drug testing showed that (a) W.B.'s organisms were not more drug resistant than three other isolates and that (b) W.B.'s organisms were more sensitive to combined quinacrine and metronidazole than to either drug alone [3].
• 4. Second, the antral uptake of the fluorescent cyclic amine, quinacrine, from the gastric lumen of pylorus-ligated rats was monitored by fluorescent microscopy and spectrophotometry and was demonstrated to be inhibited in a step-wise fashion as the luminal pH was decreased [28].
• Instead, we have found that muscarinic or histamine H1 receptor stimulation elicits the release of arachidonic acid through a quinacrine-sensitive mechanism, possibly phospholipase A2 [29].
• Mepacrine (quinacrine) and hydrocortisone inhibited and a phorbol ester enhanced both chemotaxis and phospholipase A2 activity [30].
• Eicosatetraynoic acid, an inhibitor of lipoxygenase and cyclooxygenase, and quinacrine, an inhibitor of phospholipase, prevented and reversed acetylcholine-induced relaxation, respectively, and inhibited acetylcholine-induced increased levels of cGMP [31].
• Although doxorubicin failed to induce TP53 expression or functional activity, quinacrine induced TP53 mRNA and protein expression, increased TP53 reporter activity and p21 protein expression, and induced growth inhibition in these wild-type TP53 cell lines [32].

Gene context of quinacrine

• Interruption of the yeast gene, denoted as VMA8, resulted in the null mutant delta vma8::URA3 that, like all the other V-ATPase null mutants, did not grow on medium buffered at pH 7.5 and showed no accumulation of quinacrine into their vacuoles [33].
• By screening based on these phenotypes and the inability of vma mutants to accumulate the lysosomotropic dye quinacrine in their vacuoles, five new vma complementation groups (vma41 to vma45) were identified [34].
• However, no defect in vacuolar acidification is apparent from quinacrine staining, and Gef1p co-localizes with Mnt1p in the medial Golgi [35].
• Monocyte Chemotactic Protein-1 (MCP-1), a member of the Cys-Cys branch of the chemokine superfamily, induced a mepacrine- and manoalide-sensitive increase in the release of [3H]arachidonic acid from prelabeled human monocytes and monocytic THP-1 leukemic cells [36].
• PMA elicited an inhibitory effect on PDE4D5 activity in HASMC treated with the cyclooxygenase (COX) inhibitor indomethacin, the COX-2 selective inhibitor NS-398, the phospholipase A(2) inhibitor quinacrine, and the cAMP-dependent protein kinase A (PKA) inhibitor H89 [37].

Analytical, diagnostic and therapeutic context of quinacrine

• The increased immunogenicity of L1210Ha leukemia occurring at the first transplant generation of DTIC-treated histocompatible (BALB/cCr x DBA/2Cr)F1 male mice or the appearance of strong lymphoma-associated transplantation antigens at transplant generation 6 was prevented by simultaneous administration of quinacrine [38].
• A recessive nuclear mutation, vph1-1, caused an abnormally high vacuolar pH of 6.9, as assayed by flow cytometry, and eliminated vacuolar uptake of the weak base quinacrine [39].
• Methaphase chromosomes from karyotypically normal adult humans (three males, six females) and one male with a 13p - chromosome were stained by quinacrine and then by the Ag-AS silver staining method to reveal nucleolus organizer regions (NORs) [40].
• The streptavidine-horseradish-peroxidase and DAB detection system used permitted the unequivocal identification of sperm heads with zero, one, or two hybridization signals and proved superior to either quinacrine staining or radioactive in situ hybridization [41].
• Both mutants had prolonged bleeding times accompanied by abnormalities of dense granules as determined by whole mount electron microscopy of platelets and by labeling platelets with mepacrine [42].

References