U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Showing 21 - 23 of 23 results

(+)-SKF-10,047 is a sigma-opioid receptor agonist. (+)-SKF-10,047 is distinct from its (-)-enantiomer in binding pattern and associated behavioural effects. (+)-SKF-10,047 stress-induced motor suppression, while its (-)-optical isomer was inactive. Besides activation of sigma-1 receptor, (+)-SKF-10,047 is inhibitor of Na(V)1.2 and Na(V)1.4 channels.
Veratridine (VTD), an alkaloid derived from the Liliaceae plant shows anti-tumor effects. Veratridine is also an agent that opens voltage dependent Na+ channels, blocks Na+ channel activation, and induces Ca2+ influx. The compound has been observed to be an alkaloid neurotoxin used to amplify sodium permeability. Studies report that Veratridine can trigger exocytosis and induce Ca2+ oscillations. Furthermore, Veratridine has been shown to effect the mitochondrial respiratory chain complexes, induce release of noradrenaline, and increase superoxide anion production. Veratridine competes with BTX binding in a mutually exclusive manner. However, the pharmacological effects of veratridine on Na+ channels are quite different from those of BTX. First, veratridine reduces the single Na+ channel conductance drastically whereas BTX does not. Veratridine therefore is regarded as a partial agonist and BTX as a full agonist of Na+ channels. Second, under voltage clamp conditions BTX binds practically irreversibly to Na+ channels whereas veratridine readily dissociates from its binding site. Both of these drugs, however, bind preferentially to the open state of Na+ channels. The BTX resistant Na+ channels in Phyllobates frogs remain sensitive to veratridine. The ceveratrum alkaloids, including Veratridine, have a characteristic hypotensive effect not directly involving the CNS. They slow the heart and lower arterial blood pressure by reflexly stimulating medullary vasomotor centers without decreasing cardiac output (Bezold–Jarisch effect). These agents were introduced in the 1950s as antihypertensive agents; however, they were found to have a narrow therapeutic index and their use was discontinued.
Status:
US Previously Marketed
First approved in 1999

Class (Stereo):
CHEMICAL (ABSOLUTE)


Conditions:

Levobupivacaine (CHIROCAINE®) is a (S)-enantiomer of bupivacaine and it is related chemically and pharmacologically to the amino amide class of local anesthetics. Local anesthetics block the generation and the conduction of nerve impulses by increasing the threshold for electrical excitation in the nerve, by slowing propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: 1) pain, 2) temperature, 3) touch, 4) proprioception and 5) skeletal muscle tone. Levobupivacaine (CHIROCAINE®) is a safer alternative for regional anesthesia than bupivacaine. It demonstrated less affinity and strength of depressant effects onto myocardial and central nervous vital centers in pharmacodynamic studies, and a superior pharmacokinetic profile.