LEVOBUPIVACAINE

Drug Discovery Of Levobupivacaine



Drug Discovery Of Levobupivacaine

Introduction of Levobupivacaine

The levobupivacaine is a local anesthetic to the family of amino - amides marketed under the name of Chirocaine. Levobupivacaine is the levorotatory isomer of racemic bupivacaine (Marcaina), proposed to replace the same bupivacaine because of a better safety profile on the cardiovascular system (Burlacu, Buggy, 2008, p. 381-392). It is the enantiomer levorotatory of bupivacaine. Power comparable to the latter, it seems to be associated with a decreased risk of toxicity heart (Burlacu, Buggy, 2008, p. 381-392). Like other local anesthetics, levobupivacaine block nerve conduction in sensory and motor nerves, by interacting with sodium channels in cell membranes, sensitive to electrical stimulation, but also blocks potassium channels and calcium (Burlacu, Buggy, 2008, p. 381-392). The effect appears within 15 minutes and lasts a dose-dependent. In studies conducted in surgical anesthesia, levobupivacaine produced a sensory block of up to 9 hours after epidural administration (maximum dose of 202.5 mg), lasting 6.5 hours (15 mg intrathecal) and duration 17 hours after brachial plexus block (2 mg / kg) (Burlacu, Buggy, 2008, p. 381-392). Several randomized, double-blind, have shown that the same concentration, time to onset of anesthesia, the quality and duration of sensory and motor block of levobupivacaine are similar to those of bupivacaine. The clinical overlap of the two anesthetics documented for epidural administration in abdominal surgery, in elective vascular surgery of the lower limbs and caesarean section, for spinal administration in hip arthroplasty. In the treatment of pain, analgesia obtained with epidural and intrathecal levobupivacaine was similar for the beginning and duration to that produced by bupivacaine (Burlacu, Buggy, 2008, p. 381-392).

Mechanism of Action of Levobupivacaine

Largely blocked nerve conduction in sensory and motor nerves, interacting with sodium channels in the cell membrane voltage-dependent, also blocks potassium channels and calcium. In addition, levobupivacaine interferes with impulse transmission and conduction in other tissues. Therefore, in the cardiovascular and central nervous side effects occur where major clinical. Injection dose of levobupivacaine is expressed as base, whereas the racemate bupivacaine dose is expressed as the hydrochloride. This leads to an increase of 13% or so of active ingredient in the solutions of levobupivacaine compared with bupivacaine. In clinical trials, the same nominal concentrations levobupivacaine showed a clinical effect similar to bupivacaine (Anson, Blake, et al, 2009, p. 34-35).

Target Identification and Target Validation of Levobupivacaine

The process of searching for a new drug begins by identifying the medical areas with unmet needs and identifies biological groups that can serve as a starting point for drug development viable (Ryckmans, 2009, p. 4406-4409). This would include the following:

Time: 4 to 5 years to develop preclinical phase.

Cost: The average cost of this phase amounts to approximately $ 335 million.

Analysis of substances: When you start the process, experts analyze half million substances capable of giving rise to a new drug.

Molecular biologist: Use all information on the therapeutic area and identify the proteins or enzymes involved in pathology.

Pharmacologist Chemical: Not actively participating in this preclinical phase, although their knowledge of chemistry ...