Atipamezole
[CAS# 104054-27-5]

Identification

• Classification: API >> Other chemicals
• Name: Atipamezole
• Synonyms: 4-(2-Ethyl-2-indanyl)imidazole; 4-(2-Ethyl-2,3-dihydro-1H-inden-2-yl)-1H-imidazole
• Molecular Formula: C₁₄H₁₆N₂
• Molecular Weight: 212.29
• CAS Registry Number: 104054-27-5
• SMILES: CCC1(CC2=CC=CC=C2C1)C3=CN=CN3

Properties

• Solubility: 10 mM (DMSO) (Expl.)
• Density: 1.1±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.595, Calc.^*
• Boiling Point: 367.1±11.0 °C (760 mmHg), Calc.^*
• Flash Point: 178.0±5.7 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H317-H319
• Safety Statements: P280-P305+P351+P338

Discovery and Applications

Atipamezole is a selective alpha-2 adrenergic antagonist that was first developed in the late 1980s by Orion Corporation, a Finnish pharmaceutical company. It was initially designed to reverse the sedative and analgesic effects of alpha-2 adrenergic agonists, such as medetomidine and dexmedetomidine, which are commonly used in veterinary anesthesia. The discovery of atipamezole provided an effective means of rapidly restoring consciousness and normal physiological functions following sedation in animals.

The synthesis of atipamezole involves the structural modification of imidazole derivatives to enhance its selectivity for alpha-2 adrenergic receptors. This selectivity allows atipamezole to competitively bind to these receptors, thereby counteracting the effects of alpha-2 agonists and facilitating the recovery of normal sympathetic nervous system activity. Its rapid onset of action and high efficacy make it a preferred reversal agent in veterinary medicine.

Atipamezole is primarily used in veterinary practices to reverse the sedative and analgesic effects of medetomidine and related compounds in dogs, cats, and other animals. It is administered intramuscularly and is known for its fast action in restoring mobility and responsiveness. Due to its targeted mechanism, atipamezole minimizes the risk of prolonged sedation and reduces potential cardiovascular side effects associated with alpha-2 agonists. Beyond veterinary applications, research has explored potential human applications of atipamezole, including its role in counteracting sedation in clinical settings and its potential therapeutic effects in conditions such as cognitive impairment and neuroprotection.

Ongoing research continues to investigate the broader pharmacological potential of atipamezole, including its effects on neurodegenerative diseases and its possible role in treating psychiatric disorders. While its primary application remains in veterinary medicine, future studies may expand its therapeutic utility.

References

1991. Antagonistic activities of atipamezole, 4-aminopyridine and yohimbine against medetomidine/ketamine-induced anaesthesia in cats. The Veterinary Record, 128(3), 57-60.
DOI: 10.1136/vr.128.3.57

2010. Alpha-2 Adrenergic Receptors and Attention-Deficit/Hyperactivity Disorder. Current Psychiatry Reports, 12(5), 366-373.
DOI: 10.1007/s11920-010-0136-4

2016. Effective Reversible Immobilization of Captive Himalayan Black Bears (Selenarctos thibetanus laniger) with Medetomidine-Tiletamine-Zolazepam and Atipamezole. Journal of Wildlife Diseases, 52(2), 401-404.
DOI: 10.7589/2014-08-206