Morphine-like dmgs

Perhaps the most successful modification of the 4-phenylpiperidine derivatives of morphine is the 4-anilino compounds, such as fentanyl (3.15). This dmg is 50-100 times more active than morphine, owing mainly to its excellent transport across the blood-brain barrier and into the CNS as a result of its high lipophilicity. Spectacular activities ( 5000-6000 times that of morphine) have also been achieved by introducing ether or keto substituents (sufentanil), as in the meperidine or ketobemidone series. Fentanyl derivatives are very fast acting and of short duration. They are used in neuroleptanalgesia in surgery, in combination with neuroleptics or major tranquilizers like droperidol. 

The Arrow implantable pump is non-programmable and delivers infusate (2-deoxy-5-fluorouridine, morphine sulfate, baclofen, or heparinized saline) at 3 pre-set flow rates. The pump is divided into two chambers by accordion-like movable bellows. Infusate is placed in the inner dmg reservoir chamber and Freon propellant in the outer chamber (Figure 4.19). 

It has long been known that only morphine and codeine possess analgesic properties, whereas thebaine acts as a convulsant, similar to strychnine [16]. However, analogues produced from thebaine have provided some of the more interesting and clinically useful dmgs such as buprenorphine (see Section 11.5). Indeed, an early structure-activity relationship was realized between morphine and its methylated phenolic relative, codeine. Codeine (see below) is known to have about one-tenth the analgesic activity of morphine, and was also less likely to produce addiction. Additionally, an early diacetylated analogue of morphine, heroin (6) (Fig. 11.2), demonstrated an increased potency but also an increased addictive potential. 

A study in 11 healthy subjects found that the combination of ketamine and morphine almost abolished windup-like pain (progressive increase in pain intensity on repeated stimulation) in a skin bum injury. This effect was not found with either dmg alone. Further, ketamine done, but not morphine reduced the area of secondary hyperalgesia of the local bum and increased the pain threshold, but the combination did not appear to enhance this effect. The reduction of wind-up pain may be due to ketamine-induced prevention of acute tolerance to morphine. ... 

Most of the prohibited substances are harmed because their reliably known pltys-iological effects make it likely that they could be used to gain an unfair advantage in sports. However, some of the prohibited substances such as heroin, morphine or hashish are incompatible with any sport activities. There is still an important rationale in baiming these someone under the influence of these dmgs could be a danger to themselves, their teammates or opponents. 

---