Substituted imidazoles as inhibitors of microsomal oxidation and insecticide synergists

Wilkinson, C.F.; Hetnarski, Krystyna; Hicks, L. J.

doi:10.1016/0048-3575(74)90113-8

Cited by 156 publications

(26 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is therefore, as in the rat, a very marked difference in the metabolic effects of the two aminoquinolones. We have previously suggested (Back etal., 1983) that the most probable explanation is a structure-activity phenomenon similar to that highlighted for the imidazole group of compounds (Wilkinson et al, 1972(Wilkinson et al, , 1974Rogerson et al, 1977). The approximately two-fold increase in the 'initial' (0-24 h) half-life of antipyrine by PQ is a reflection of the amount of inhibitor present and the inhibitor constant.…”

Section: Resultsmentioning

confidence: 93%

Effect of chloroquine and primaquine on antipyrine metabolism.

Back¹,

Purba²,

Park³

et al. 1983

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 The effects of two antimalarial drugs, chloroquine and primaquine on antipyrine kinetics and metabolism have been studied in volunteers. 2 Chloroquine (250 mg) given 2 h before antipyrine (600 mg orally) had no effect on salivary kinetics of antipyrine or on the urinary recovery of metabolites. Primaquine (45 mg) given 2 h before antipyrine (300 mg orally), increased antipyrine half-life (calculated from 0-24 h) from 12.7 + 3.2 (mean + s.d.) to 25.3 + 3.9hand decreased clearance from3.01 + 0.67 to 1.32 + 0.321 h-. There was no change in the apparent volume of distribution. Antipyrine half life changed with time in the presence of primaquine and when calculated between 24 and 48 h had returned to control. 3 After primaquine, the metabolic clearance (calculated from 0-24 h) of antipyrine to its three main metabolites, 3-hydroxymethylantipyrine, 4-hydroxyantipyrine and norantipyrine was significantly reduced. There was no selective effect on a particular metabolic pathway.4 There was no change in 6,8-hydroxycortisol excretion (expressed as a ratio of total 17-hydroxycorticosteroids) in the period 0-48 h following primaquine administration. 5 The inhibition of hepatic metabolism by primaquine but not the structurally related chloroquine may be an example of a structure activity phenomenon and could be of clinical significance.

show abstract

Section: Resultsmentioning

confidence: 93%

Effect of chloroquine and primaquine on antipyrine metabolism.

Back¹,

Purba²,

Park³

et al. 1983

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…The phenylbutazone-interaction has been the most extensively studied O'Reilly et al, 1980;Banfield et al, 1983) and it appears that there is a complex effect on both enantiomers involving inhibition of metabolism as well as displacement from plasma proteins. Cimetidine is a substituted imidazole and is thus thought to be a potent inhibitor of drug oxidation (Wilkinson et al, 1974;Somogyi & Gugler, 1982). This has in fact been shown to occur with antipyrine (Serlin et al, 1979), diazepam (Klotz & Reimann, 1980), phenytoin (Hetzel etal., 1981) and theophylline (Jackson et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

Stereoselective interaction between the R enantiomer of warfarin and cimetidine.

Choonara¹,

Cholerton²,

Haynes³

et al. 1986

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 The stereoselectivity of the pharmacokinetic interaction between warfarin and cimetidine was investigated in eight healthy volunteers. 2 The warfarin enantiomers were given separately as single doses (15 mg) alone and during chronic administration of cimetidine (1 g day-1). 3 Cimetidine did not interact with S warfarin but there was an interaction with the R enantiomer of warfarin. Cimetidine caused a significant increase in the mean plasma halflife of R warfarin (from 47.8 h to 57.8 h) and a significant decrease in its mean plasma clearance (from 2.3 to 1.7 ml h-1 kg-') (P < 0.02). 4 Administration of a pharmacological dose of vitamin K1 together with the enantiomers of warfarin was necessary clinically and resulted in elevation of vitamin K1 2,3-epoxide concentrations, which were similar in each case.

show abstract

“…However, a closely related substance, 4(5)-(benzylthiomethyl)-1H-imidazole (which has the structure of CC12 without the iodosubstituent), was reported to be a weak inhibitor of histamine synthesis (Swett and Yellin, 1970), and an inhibitor of microsomal drug oxidation (Wilkinson et al, 1974;Wilkinson et al, 1972). Interactions between imidazole-containing histamine antagonists and some cytochrome P-450 proteins are well known (Szutowski et al, 2002,Alves-Rodrigues et al, 1996.…”

Section: Discussionmentioning

confidence: 99%

CC12, a high-affinity ligand for [3H]cimetidine binding, is an improgan antagonist

Hough

Nalwalk

Phillips³

et al. 2007

Neuropharmacology

View full text Add to dashboard Cite

SummaryImprogan, a chemical congener of cimetidine, is a highly effective non-opioid analgesic when injected into the CNS. Despite extensive characterization, neither the improgan receptor, nor a pharmacological antagonist of improgan has been previously described. Presently, the specific binding of 3 H-cimetidine (3HCIM) in brain fractions was used to discover 4(5)-((4-iodobenzyl) thiomethyl)-1H-imidazole, which behaved in vivo as the first improgan antagonist. The synthesis and pharmacological properties of this drug (named CC12) are described herein. In rats, CC12 (50 -500 nmol, icv) produced dose-dependent inhibition of improgan (200 -400 nmol) antinociception on the tail flick and hot plate tests. When given alone to rats, CC12 had no effects on nociceptive latencies, or on other observable behavioral or motor functions. Maximal inhibitory effects of CC12 (500 nmol) were fully surmounted with a large icv dose of improgan (800 nmol), demonstrating competitive antagonism. In mice, CC12 (200-400 nmol, icv) behaved as a partial agonist, producing incomplete improgan antagonism, but also limited antinociception when given alone. Radioligand binding, receptor autoradiography, and electrophysiology experiments showed that CC12's antagonist properties are not explained by activity at 25 sites relevant to analgesia, including known receptors for cannabinoids, opioids or histamine. The use of CC12 as an improgan antagonist will facilitate the characterization of improgan analgesia. Furthermore, because CC12 was also found presently to inhibit opioid and cannabinoid antinociception, it is suggested that this drug modifies a biochemical mechanism shared by several classes of analgesics. Elucidation of this mechanism will enhance understanding of the biochemistry of pain relief.

show abstract

Substituted imidazoles as inhibitors of microsomal oxidation and insecticide synergists

Cited by 156 publications

References 17 publications

Effect of chloroquine and primaquine on antipyrine metabolism.

Effect of chloroquine and primaquine on antipyrine metabolism.

Stereoselective interaction between the R enantiomer of warfarin and cimetidine.

CC12, a high-affinity ligand for [3H]cimetidine binding, is an improgan antagonist

Contact Info

Product

Resources

About