There was no observable tolerance during a four weeks course of treatment with daily administration of oxcarbazepine or licarbazepine in electroshock test on mice and rats. Most of the antiepileptic activity can be attributed to licarbazepine. Aside from its reduction in side effects, it is presumed to have the same main mechanism as carbamazepine, sodium channel inhibition, and is generally used to treat the same conditions. Pharmacogenetics
The human leukocyte antigen (HLA) allele B*1502 has been associated with an increased incidence of Stevens–Johnson syndrome and toxic epidermal necrolysis in people treated with carbamazepine, and thus those treated with oxcarbazepine might have similar risks. People of Asian descent are more likely to carry this genetic variant, especially some Malaysian populations, Koreans (2%), Han Chinese (2–12%), Indians (6%), Thai (8%), and Philippines (15%). Therefore, it has been suggested to consider genetic testing in these people prior to initiation of treatment. Structure
Oxcarbazepine is a structural derivative of carbamazepine, with a ketone in place of the carbon–carbon double bond on the dibenzazepine ring at the 10 position (10-keto). This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia or agranulocytosis occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine — sodium channel inhibition (presumed to be the main mechanism of action) – and is generally used to treat the same conditions. Oxcarbazepine is a prodrug which is activated to licarbazepine in the liver.
Pharmacology
Systemic absorption of the globular tetradecapeptide is minimal.Linaclotide, like the endogenous guanylin and uroguanylin it mimics, is an agonist that activates the cell surface receptor of guanylate cyclase 2C (GC-C). The medication binds to the surface of the intestinal epithelial cells. Linaclotide is minimally absorbed and it is undetectable in the systemic circulation at therapeutic doses. Activation of GC-C increases cyclic guanosine monophosphate (cGMP). Elevated cGMP stimulates secretion of chloride and bicarbonate and water into the intestinal lumen, mainly by way of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel activation. This results in increased intestinal fluid and accelerated transit. By elevating cGMP, linaclotide is also considered to reduce activation of colonic sensory neurons, reducing pain; and activates colonic motor neurons, which increases smooth muscle contraction and thus promotes bowel movements. Chemistry
Linaclotide is a hybrid peptide design of the E.coli heat-stable enterotoxin (STa) and the endogenous peptide hormones endogenous guanylin and uroguanylin.