012-Adrenoceptor Agonist Research Paper
History
The use of α2-adrenoceptor agonists in human medicine is not new and has been in practice for decades. In the early 1960’s, the first α2-adrenoceptor agonist was synthesized to be used as a nasal decongestant. Early application of the new substance, now known as clonidine, showed unexpected side effects, with sedation for 24 hours and symptoms of severe cardiovascular depression.[6] An imidazoline derivative Clonidine hydrochloride, after subsequent testing was introduced as an antihypertensive drug in 1966.[8] Veterinarians employed xylazine and detomidine to induce analgesia and sedation in animals since 1970.[8,9] DEX a 2nd generation α2 adrenergic receptor specific, pharmacologically active D- isomer of medetomidine was first synthesized
in late 1980’s. Phase 1 studies were completed in early 1990’s, while clinical trials began in late 1990’s. DEX was approved by the Food and Drug Administration at the end of 1999 initially as an ICU sedative.[10] By 2000 it became alpha -2 agonist of choice, due to its greater alpha- 2: alpha- 1 affinity (approximately1620:1 for meditomedine vs 220:1 for clonidine and 160:1 for xylazine). [11, 12] This increased selectivity results in more predictable and effective sedation and analgesia and fewer side effects. [13] In late 2008, the FDA approved the use of dexmedetomidine for nonintubated patients requiring sedation prior to and/or during surgical and other procedures. [14] Currently many countries have granted approval for prolonged use of dexmedetomidine at varying doses (0.1–2.5 μg/kg/hour) and durations up to 30 days. [15]
The use of α2-adrenoceptor agonists in human medicine is not new and has been in practice for decades. In the early 1960’s, the first α2-adrenoceptor agonist was synthesized to be used as a nasal decongestant. Early application of the new substance, now known as clonidine, showed unexpected side effects, with sedation for 24 hours and symptoms of severe cardiovascular depression.[6] An imidazoline derivative Clonidine hydrochloride, after subsequent testing was introduced as an antihypertensive drug in 1966.[8] Veterinarians employed xylazine and detomidine to induce analgesia and sedation in animals since 1970.[8,9] DEX a 2nd generation α2 adrenergic receptor specific, pharmacologically active D- isomer of medetomidine was first synthesized
in late 1980’s. Phase 1 studies were completed in early 1990’s, while clinical trials began in late 1990’s. DEX was approved by the Food and Drug Administration at the end of 1999 initially as an ICU sedative.[10] By 2000 it became alpha -2 agonist of choice, due to its greater alpha- 2: alpha- 1 affinity (approximately1620:1 for meditomedine vs 220:1 for clonidine and 160:1 for xylazine). [11, 12] This increased selectivity results in more predictable and effective sedation and analgesia and fewer side effects. [13] In late 2008, the FDA approved the use of dexmedetomidine for nonintubated patients requiring sedation prior to and/or during surgical and other procedures. [14] Currently many countries have granted approval for prolonged use of dexmedetomidine at varying doses (0.1–2.5 μg/kg/hour) and durations up to 30 days. [15]