Analgesics, centrally acting

Acetaminophen is a centrally acting analgesic that produces analgesia by inhibiting prostaglandin production in the brain and spinal cord. It is an effective and inexpensive analgesic with a favorable risk-benefit profile.9 It should be tried initially at an adequate dose and duration before considering an... 

Tramadol, a centrally acting analgesic for moderate to moderately severe pain, binds to jl opiate receptors and weakly inhibits norepinephrine and serotonin reuptake. 

A common strnctnral feature required for centrally acting analgesic activity in the opioids is the combination of an aromatic ring and a piperidine ring that maintains the stereochemistry at the chiral centre, as shown below. 

Tramadol Acute intoxication with alcohol, hypnotics, narcotics, centrally acting analgesics, opioids, or psychotropic drugs. 

Tramadol is a central-acting analgesic, effective for mild to moderate acute and chronic pain. It impairs nociception by a unique mechanism that is not completely understood. In animal models, it binds to the /u. opioid receptor and is a weak inhibitor of serotonin and norepinephrine reuptake, actions similar to those ascribed to the SSRIs and TCAs. Seizures have been reported in patients taking tramadol. Abuse potential is low, but does exist. 

III.b.3. Some Comments on Potent Centrally Acting Analgesics (See Tables 4 and 5)... 

Analgesic efficacy and clinical use Tramadol HCI (Friderichs et al., 1978 Raffa and Friderichs, 1996) is a centrally-acting analgesic with a p-opioid and non-opioid component of action (Raffa et al., 1992). The non-opioid component induces inhibition of spinal pain transmission via inhibition of noradrenaline (NA) and serotonin (5HT) re-uptake (Driessen and Reimann, 1992 Driessen et al. 1993) Tramadol is a racemate and uptake inhibition and opioid properties are differentially distributed between the enantiomers (Raffa et al., 1993) and the active O-desmethyl metabolite. p-Opioid receptor binding, NA uptake inhibition and 5HT uptake inhibition are regarded as the relevant (Desmeules et al., 1996 Raffa and Friderichs, 1996) components of the complex analgesic action profile of the compound (+)-0-desmethyl-tramadol mainly contributes to p-activity, (-)-tramadol to NA uptake inhibition and (+)-tramadol to 5HT uptake inhibition, respectively. 

Tramadol is a potent analgesic (Lee et al., 1993). The compound is marketed worldwide and has become one of the most important centrally-acting analgesics (Bamigbade, 1998 Scott and Perry, 2000) for the treatment of acute and chronic moderate to severe pain. 

Codd, E. E., Shank, R. P., Schupsky, J. J., Raffa, R. B. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics structural determinants and role in antinociception, J. Pharmacol. Exp. Ther. 1995, 274, 1263-1270. 

Grunenthal s interest in pain research started in 1962, when Kurt Flick designed a simple molecule containing the essential structural elements of morphine to be a potent analgesic. This prediction was clinically confirmed and today this compound -tramadol - is one of the leading centrally acting analgesics. 

In recent years there has been a major research effort, so far without success, to produce potent, centrally acting analgesics that do not have an abuse potential. The discovery of various types of opioid receptor, which may have different effects on central neurotransmitter function, may ultimately lead to the development of such a drug. In the meantime, the most widely used opioids, for example morphine, heroin (also called diacetylmorphine) and codeine are therapeutically effective but are liable to be abused and produce dependence. The structure of some of the morphine-like analgesics and their antagonists are shown in Figure 15.2. 

This centrally acting analgesic agent242, ethyl 2-amino 6 [(4-fluorophenyl)methyl] amino -3-pyridinyl-2,6-14C carbamate maleate, 238, has been 14C-labelled243 in nine steps starting with potassium cyanide[14C] and 1,3-dibromopropane (equation 100). 

The peripherally acting and centrally acting analgesics are the mainstay of pain management in outpatient practice. The most useful agents in each class are discussed in the following sections. 

Lewis KS, Han NH. Tramadol a new centrally acting analgesic. AmJ Health Syst Pharm 1997 54 643-652. 

Flupirtine is a non-opiate, centrally acting analgesic, with muscle relaxant properties. It causes predominantly nervous system adverse effects (visual, disorientation, confusion, tremor). About 26% of patients develop minor adverse reactions (1). 

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