Other Centrally Active Analgesics

Fentanyl and its derivatives are currently seldom abused, or at least such abuse tends not to be noticed. The same applies to pethidine and the other opiates/ opioids. However, changes in the drug scene could quickly lead to a change here also. 

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Apart from Valoron N , this substance is the only centrally active analgesic that is not prohibited by the BtmW. Abusers are sometimes found among medicament-dependent patients who additionally consume other substances such as peripherally active analgesics, benzodiazepines or antidepressants. This substance is not common in the drug scene, and frequency of abuse shows large regional variations. 

SAFETY PROFILE Poison by ingestion, subcutaneous, intramuscular, intraperitoneal, and intravenous routes. Experimental reproductive effects. Human systemic effects by intramuscular and intravenous routes wakefulness, euphoria, hallucinations or distorted perceptions, tremors, convulsions, excitement, motor activity changes, muscle weakness, analgesia, withdrawal, parasympathomimetic effects, nausea or vomiting, and dermititis. Can cause drug dependency and other central nervous system effects. An analgesic. When heated to decomposition it emits toxic fumes of NOx. See also ALLYL COMPOUNDS. 

Further variations on the imidazoline nucleus may )deld compounds with less potent hypotensive or sedative properties, whilst retaining other central m-pathomimetic activity including the analgesic activity. An example of such a compound is St-567 (7) which displays a ratio of hypotensive activity to antinociceptive activity in rabbits some eight times more favourable than with clonidine [28],... 

Neuropathic pain is initiated or caused by a primary lesion in the peripheral or central nervous system. The causative agent may be trauma, nerve-invading cancer, herpes zoster, HIV, stroke, diabetes, alcohol or other toxic substances. Neuropathic pain is refractory to most analgesic drugs. Altered sodium channel activity is characteristics of neuropathic pain states. 

This peripheral activity may be a rational basis for the use of systemic local anaesthetics in neuropathic states since ectopic activity in damaged nerves has been shown to be highly sensitive to systemic sodium channel blockers. This too is probably part of the basis for the analgesic effects of established effective anti-convulsants that block sodium channels such as carbamazepine, although central actions are important and may even predominate. The precise actions of excitability blockers therefore remains hazy as does any clear basis for the effectiveness of antidepressants and other adrenergic agents in the treatment of neuropathic pain as both central and peripheral actions, including sympathetic effects are possible. 

Additional in vivo studies on the biological activity of proanthocyani-dins investigating a series of behavioral activities (motihty, body weight gain, body temperature, motoric coordination, anticonvulsant effects and central analgesic activities) showed no or only moderate pharmacological effects [53]. On the other hand, dietary supplementation with cocoa pro-cyanidin supplements can dose-dependently prevent the development of hyperglycemia in diabetic obese mice [54]. 

Hydrochlorides of dibenzazonines 14b, 106,107, and 108 have been tested by Pecherer and Brossi (29) for analgesic and anti-inflammatory activity, antiappetite and blood pressure effects, and activity against a series of infections. The alkaloid protostephanine (3) exerts a moderately strong and persistent hypotensive effect. Most of the other compounds show some central nervous activity. Independent studies have also found CNS activity for compounds 107, 109, and 110, all of which behave as hypotensive agents (30). 

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