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pecification

CAS No.	36309-01-0
Molecular Formula	C18H25N
Molecular Weight	255.4 g/mol
IUPAC Name	(1S,9S,10S)-4,17-dimethyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene
Standard InChI	InChI=1S/C18H25N/c1-13-6-7-14-12-17-15-5-3-4-8-18(15,16(14)11-13)9-10-19(17)2/h6-7,11,15,17H,3-5,8-10,12H2,1-2H3/t15-,17+,18+/m1/s1
Standard InChI Key	KBEZZLAAKIIPFK-NJAFHUGGSA-N
Isomeric SMILES	CC1=CC2=C(C[C@H]3[C@@H]4[C@]2(CCCC4)CCN3C)C=C1
SMILES	CC1=CC2=C(CC3C4C2(CCCC4)CCN3C)C=C1
Canonical SMILES	CC1=CC2=C(CC3C4C2(CCCC4)CCN3C)C=C1

Introduction

 

Chemical Profile and Structural Characteristics

Molecular Architecture

Dimemorfan (CAS Registry Number: 36309-01-0) possesses a complex polycyclic structure characteristic of morphinan derivatives. The base compound, with the systematic name (9α,13α,14α)-3,17-dimethylmorphinan, features a molecular formula of C18H25NC18H25N and a molecular weight of 255.40 g/mol  . Its phosphate salt form (CAS 36304-84-4), marketed as Astomin®, increases water solubility while maintaining biological activity, with a molecular weight of 353.39 g/mol  .

Table 1: Key Chemical Properties

The stereochemical configuration plays a crucial role in its pharmacological activity, with absolute stereochemistry confirmed through X-ray crystallography . The SMILES notation $\text{OP(O)(O)=O.CN1CC[C@@]23CCCC[C@@H]2[C@@H]1CC4=C3C=C(C)C=C4}$ precisely describes its three-dimensional arrangement .

Synthetic Pathways

Pharmacological Mechanisms

Central Antitussive Action

Dimemorfan exerts its therapeutic effect through direct action on the cough center in the medulla oblongata, independent of opioid receptor pathways . Animal studies demonstrate that its antitussive activity remains unaffected by naloxone pretreatment, confirming the non-narcotic nature of its mechanism  . Electrophysiological recordings in feline models revealed 73% suppression of cough reflexes at doses of 2 mg/kg .

Therapeutic Efficacy

Comparative Clinical Trials

Three pivotal randomized controlled trials established dimemorfan’s position in cough management:

Table 2: Clinical Trial Outcomes (N=1,842 patients)

The post-marketing surveillance data (n=12,459) revealed 83% physician-reported effectiveness, with particular utility in chronic bronchitis cases .

Pediatric Formulations

The syrup formulation maintains pharmacokinetic equivalence to tablet forms:

• TmaxTmax: 2.1 ± 0.8 hrs
• CmaxCmax: 5.3 ± 1.2 μg/L (40 mg dose)
• AUC0−240−24: 57.26 μg·h/L

Dose proportionality studies confirmed linear pharmacokinetics between 10-40 mg ranges .

Pharmacokinetic Considerations

Absorption and Distribution

• Bioavailability: 89% ± 12% (20 mg tablet)
• Protein Binding: 64-68% (pH-dependent)
• Volume of Distribution: 5.3 L/kg

Food interaction studies showed 32% increased AUC under high-fat conditions, necessitating consistent dosing timing .

Metabolic Pathways

Hepatic metabolism proceeds via three primary routes:

• CYP3A4-mediated N-demethylation (42%)
• CYP2D6-mediated hydroxylation (29%)
• Glucuronidation (19%)

The elimination half-life of 6.8 ± 1.3 hours supports TID dosing regimens without accumulation