Denzimol hydrochloride
Denzimol hydrochloride is an orally active anticonvulsant agent. Denzimol hydrochloride inhibits cytochrome P450, and interacts with benzodiazepine receptors. Denzimol hydrochloride selectively antagonizes tonic components of Metrazol-induced seizures in rats and mice. Denzimol hydrochloride can be used for the research of epilepsy and convulsions.
For research use only. We do not sell to patients.
- CAS No.: 77234-90-3
- Formula: C19H21ClN2O
- Molecular Weight:328.84
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Denzimol hydrochloride binds reversibly to rat liver microsomal cytochrome P450 as a type II ligand with a Ks value of 6.66 mM[1].
Denzimol (10-10-10-4 M; 20 min) hydrochloride inhibits rat liver microsomal Carbamazepine (HY-B0246) 10,11-epoxidation, Diazepam C3-hydroxylation, and Diazepam N1-dealkylation with IC50 values of 4.26 × 10-7 M, 1.44 × 10-6 M, and 6.66 × 10-7 M, respectively[1].
Denzimol hydrochloride does not alter the plasma protein binding of diazepam in pooled rat serum in vitro[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Denzimol (5 mg/kg; p.o.; single dose; 15 minutes prior to Diazepam injection) hydrochloride significantly increases diazepam plasma and brain concentrations in rats by reducing diazepam's total plasma clearance by ~40%, resulting in an 1.8-fold higher plasma AUC0-t and doubled brain diazepam concentrations[2].
Denzimol (up to 289 mg/kg; i.p.; single dose) hydrochloride selectively antagonizes tonic components of Metrazol-induced seizures in rats, with an ED50 of 2.02 mg/kg for protection against tonic hindpaw extension, and shows no activity against clonic seizures at doses up to 260 mg/kg[4].
Denzimol (up to 182 mg/kg; p.o.; single dose) hydrochloride selectively antagonizes tonic components of Metrazol-induced seizures in mice, with an ED50 of 8.8 mg/kg for protection against tonic hindpaw extension, and shows no activity against clonic seizures at doses up to 182 mg/kg[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD-COBS rats (male, 200-300 g)[1]
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Dosage:15 mg/kg (CBZ disposition study); 0.94, 1.87, 3.75, 7.50, 15.0 mg/kg (pentobarbitone sleeping time study)
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Administration:p.o.; single dose; 30 minutes before CBZ injection (CBZ disposition study); p.o.; single dose; 1 hour before pentobarbitone injection (pentobarbitone sleeping time study)
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Result:Reduced CBZ total plasma clearance from 15.3 mL/min/kg to 9.9 mL/min/kg.
Prolonged CBZ elimination half-life from 83 minutes to 134 minutes.
Caused non-significant increase in CBZ-E elimination half-life from 184 minutes to 240 minutes.
Caused non-significant reductions in CBZ-E peak plasma concentrations from 14 nmol/mL to 11 nmol/mL and time to maximum CBZ-E concentrations from 132 minutes to 202 minutes.
Prolonged pentobarbitone sleeping time.
Achieved an ED50 of 3.0 mg/kg for doubling or more of control sleeping time.
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Animal Model:CD-COBS (male, 270-300 g)[2] 5 mg/kg
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Dosage:5 mg/kg
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Administration:p.o.; single dose; 15 minutes prior to diazepam injection
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Result:Increased plasma diazepam concentrations throughout the 180-minute sampling period, resulting in a 1.8-fold increase in plasma area under the curve (AUC).
Reduced total plasma clearance of diazepam by ~40%.
Doubled diazepam brain concentrations compared to controls at both 60 minutes and 180 minutes.
Had no significant effect on diazepam's apparent volume of distribution, elimination half-life, or plasma protein binding.
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Animal Model:Sprague-Dawley (female, 110-130 g, maximal metrazol/PTZ-induced seizures model)[4]
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Dosage:up to 289 mg/kg
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Administration:i.p.; single administration
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Result:Achieved an ED50 of 2.02 mg/kg for protection against tonic hindpaw extension.
Achieved an ED50 of 22.5 mg/kg for protection against tonic forepaw extension.
Showed no measurable ED50 for protection against twitches/tremors or clonic seizures at doses tested.
Achieved an ED50 of 289 mg/kg for induction of ataxia.
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Animal Model:Sprague-Dawley (female, 110-130 g, maximal metrazol/PTZ-induced seizures model)[4]
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Dosage:up to 182 mg/kg
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Administration:p.o.; single dose
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Result:Achieved an ED50 of 8.8 mg/kg for protection against tonic hindpaw extension.
Achieved an ED50 of 20.2 mg/kg for protection against tonic forepaw extension.
Showed no measurable ED50 for protection against twitches/tremors or clonic seizures at doses tested.
Achieved an ED50 of 146.1 mg/kg for induction of ataxia.
Chemical Information
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CAS No. 77234-90-3
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Molecular Weight 328.84
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Formula C19H21ClN2O
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SMILES
OC(C1=CC=C(CCC2=CC=CC=C2)C=C1)CN3C=CN=C3.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Salmona M, et al. Interaction of the anticonvulsants, denzimol and nafimidone, with liver cytochrome P450 in the rat. J Pharm Pharmacol. 1988;40(1):17-21. [Content Brief]
[2]. Caccia S, et al. Effect of the anticonvulsant denzimol on the disposition of diazepam in the rat. J Pharm Pharmacol. 1986 Jun;38(6):469-72. [Content Brief]
[3]. Patsalos PN, et al. The interaction of denzimol (a new anticonvulsant) with carbamazepine and phenytoin. J Neurol Neurosurg Psychiatry. 1985 Apr;48(4):374-7. [Content Brief]
[4]. Ibba M, et al. Differential antagonism of denzimol to various components of metrazol-induced seizures in rats and mice. Pharmacol Res Commun. 1985 Dec;17(12):1169-80. [Content Brief]
[5]. Bertin D, et al. Determination of denzimol, a new anticonvulsant agent, and its main metabolite in biological material by gas chromatography and high-performance liquid chromatography. J Chromatogr. 1986 May 28;378(1):147-54. [Content Brief]
[6]. Benassi E, et al. Preliminary note on the effect of denzimol in partial epilepsy. Ital J Neurol Sci. 1988 Aug;9(4):331-5. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Denzimol hydrochloride Related Classifications
HY-105059A Related Classifications
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