Structure activity relationships in the pruritogenicity of chloroquine and amodiaquine metabolites in a dog model

Osifo, Nosakhare G.

doi:10.1016/0923-1811(91)90017-r

Cited by 8 publications

(9 citation statements)

References 12 publications

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“…The substances in our study were injected intradermally, which mirrored studies in humans and mice where the same substances were evaluated. Many previously published studies on the induction of pruritus in dogs used systemic (intravenous) or intra‐cisternal administration of chemicals to induce pruritus, rather than cutaneous, and many of these substances caused neurological signs or death in addition to other systemic signs 24–28 and therefore cannot be compared with our study. To our knowledge, only three studies have been published on the cutaneous administration of pruritus‐producing substances in dogs 7,24,25 .…”

Section: Discussionmentioning

confidence: 99%

Investigation of the pruritogenic effects of histamine, serotonin, tryptase, substance P and interleukin‐2 in healthy dogs

Carr

Torres

Koch

et al. 2009

Veterinary Dermatology

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There are numerous studies of the pruritus-producing effects of histamine, serotonin, tryptase, substance P and interleukin-2 in humans and mice, but very little reported in dogs even though a common reason dogs are presented to veterinarians is pruritus. The aim of this study was to determine whether substances known to cause pruritus in humans also cause pruritus in dogs. Twenty-five clinically healthy research beagle dogs were included in the study. All dogs first received an intradermal injection of 0.05 mL saline as a control substance and were video-recorded for 20 min before and after the injection. Twenty-four hours later the dogs were randomly divided into five groups of five dogs each and randomly assigned to receive histamine, serotonin, tryptase, substance P or interleukin-2 injected intradermally each at the volume of 0.05 mL. On subsequent days, increasing concentrations of each substance were used. Before (baseline) and after the injection of each concentration of the substances, the dogs were video-recorded for 20 min. The frequency and character of pruritus episodes (scratching, licking, chewing, rubbing or rolling) were noted and these data were used for statistical analysis. The number of pruritus episodes was compared among baseline, saline and the different concentrations of each substance. The results showed that dogs did not have a significant increase in pruritic behaviour above baseline or saline after injection of any of the investigated substances (generalized linear model; P = 0.23).

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Section: Discussionmentioning

confidence: 99%

Investigation of the pruritogenic effects of histamine, serotonin, tryptase, substance P and interleukin‐2 in healthy dogs

Carr

Torres

Koch

et al. 2009

Veterinary Dermatology

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“…The antimalarial chloroquine (CQ) can induce pruritus in dogs after femoral artery ligation [Osifo, ]. We have followed up on this observation and investigated the pruritic activity of CQ in dogs, using various routes of administration to develop a canine model of pruritus.…”

Section: Introductionmentioning

confidence: 99%

Characterization and Validation of a Canine Pruritic Model

Åberg

Arulnesan

Bolger

et al. 2015

Drug Development Research

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Preclinical Research The mechanisms mediating canine pruritus are poorly understood with few models due to limited methods for inducing pruritus in dogs. Chloroquine (CQ) is a widely used antimalarial drug that causes pruritus in humans and mice. We have developed a canine model of pruritus where CQ reliably induced pruritus in all dogs tested following intravenous administration. This model is presently being used to test antipruritic activity of drug candidate molecules. This publication has been validated in a blinded cross-over study in eight beagle dogs using the reference standards, oclacitinib and prednisolone, and has been used to test a new compound, norketotifen. All compounds reduced CQ-induced pruritus in the dog. The sensitivity of the model was demonstrated using norketotifen, which at three dose levels, dose-dependently, inhibited scratching events compared with placebo.

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“…An animal model of chloroquine-related pruritus [12], which recently revealed a structure-activity relationship among chloroquine and amodiaquine metabolites in their pruritogenic activities [11], has also supported the pathophysiological basis of MAAP.…”

Section: Introductionmentioning

confidence: 99%

“…The search for the mechanisms involved in the aggravation of chloroquine-related itch, and possible palliatives to improve the compliance of malarial patients with the 4aminoquinoline based regimens [2,[6][7][8][9][10][11][12], has led to the emergence of two schools of thought on the mechanisms involved.…”

Section: Introductionmentioning

confidence: 99%

“…The second and more recent school of thought on the mechanisms of MAAP considers the pathophysiology of malaria and the associated pyrogenic haemodynamics for generating hyperpyrexia, via chills and rigors, in the hot tropical African climate, and relates the ischaemic stress, imposed on the skin during these elements of malarial fever thermogenesis, to a priming effect on the skin for enhanced pruritogenicity of chloroquine in malaria patients [2]. An animal model of chloroquine-related pruritus [12], which recently revealed a structure-activity relationship among chloroquine and amodiaquine metabolites in their pruritogenic activities [11], has also supported the pathophysiological basis of MAAP.…”

Section: Introductionmentioning

confidence: 99%

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Drugs against chloroquine antimalarial itch

Asawalam

Osifo

Haller

1993

Acad Dermatol Venereol

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Bacl^round Limb activity meters are useful in correlation with subjective measurements for studying the antipruritic effects of drugs against current chloroquine itch among patients with malarial fever, in a tropical environment. Objective To prospectively monitor the palliative effects of drugs, without any presumptively significant antipuritic effects known, against moderate to severe chloroquine-related pruritus among patients with malaria. Methods Using a standard ordinal (0-10) scale questionnaire and limb activity meters on all limbs, 60 subjects (50 malarial patients plus 10 healthy controls; both sexes; aged 16-32 years) were recruited for study. Forty patients and the 10 healthy unmedicated controls completed the study and were used for data analysis. Results Dapsone (50 mg tablets, 8 hourly, orally) significantly reduced pruritus ordinal scores (below 2.5) and limb activity recordings to levels comparable with unmedicated controls by the second or third night of nocturnal monitoring the chloroquine itch among the patients. Clemastine or ketotifen (1 mg tablets, 8 hourly, orally) or prednisolone (5 mg tablets, 12 hourly, for 3 days, then tapered to 5 mg daily for another 2 days, orally), did not significantly exceed the placebo responsiveness to vitamin B-complex tablets (one 8 hourly, orally, for 3 days). Conclusion Dapsone, or sulphapyridine (500 mg tablets, 6 hourly, orally daily for 5 days in another recent investigation) have now emerged as potent symptomatic palliatives against chloroquine pruritus.

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Structure activity relationships in the pruritogenicity of chloroquine and amodiaquine metabolites in a dog model

Cited by 8 publications

References 12 publications

Investigation of the pruritogenic effects of histamine, serotonin, tryptase, substance P and interleukin‐2 in healthy dogs

Investigation of the pruritogenic effects of histamine, serotonin, tryptase, substance P and interleukin‐2 in healthy dogs

Characterization and Validation of a Canine Pruritic Model

Drugs against chloroquine antimalarial itch

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