Meperidine, structure

Fentanyl is a synthetic opioid analgesic, introduced in the 1950s, that has enhanced analgesic activity and potency and fewer adverse effects compared with morphine or meperidine. Structurally related to meperidine, fentanyl gained wide popularity as an intra-operative anesthetic adjunct as well as an effective analgesic for the management of acute and chronic pain. 

Exploratory research on structure activity relationships in the meperidine series revealed the interesting fact that the oxygen atom and carbonyl group of this molecule could often be interchanged. That is, the so-called "reversed meperidine" (C) still exhibits analgesic activity in experimental animals. (Note that, except for the interchange, the rest of the molecule is unchanged.)... 

Still further simplification of the structural requirements for central analgesic activity came from the serendipitous observation that the simple phenyl pi peri dine, meperidine... 

The search for opioid analgesics which show reduced addiction liability ha.s centered largely on benzomorphan and morphinan derivatives. Some research has, however, been devoted to derivatives of the structurally simpler meperidine series. The preparation of one such compound, picenadol (59), starts with the reaction of N-methyl-4-piperidone with the lithium derivative from m-methoxybromobenzene. Dehydration of the first formed carbinol 51 gives the intermediate 52. Deprotonation by means of butyl lithium gives an anion which can be depicted in the ambident form 53. In the event, treatment of the anion with propyl bromide gives the product 54 from reaction of the benzylic anion. Treatment of that product, which now contains an eneamine function. 

Extensive molecular dissection of the morphine molecule over the past several decades led to a host of molecules which showed narcotic analgesic activity even though they possessed but faint suggestion of the structural features present in morphine itself. Thus, both cyclic molecules such as meperidine (70) and alphaprodine (71), and acyclic Compounds such as methadone (72) were found to be effective analgesics. Common features of these compounds were formalized by the Beckett-Casy rule, which states as minimal required structural features (a) an aromatic ring attached to... 

Figure 7.4 The chemical structure of meperidine, its analogue MPPP, and the closely related neurotoxin MPTP, are all shown here. Meperidine, an anesthetic, was also used as an alternative to morphine. It proved advantageous because it has a shorter length of duration and fewer side effects than morphine.

This drug is a structural analog of meperidine and loperamide however, it practically duplicates all of the pharmacological properties of loperamide. Being analogous to loperamide, it is mainly used for treating diarrhea. Synonyms for this drug are fentanest, lep-rofen, and others. 

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

Loperamide is also structurally related to meperidine and its mechanism of action is like diphenoxylate. Gastointestinal motility is decreased by inhibition of the contractions of the longimdinal as well as the circular musculature, and the activity of this agent is at least in part mediated by its affinity for opiate receptors. As it hardly crosses the blood-... 

The first agent of this class to be introduced in the clinic, haloperidol (18-8), interestingly shares the 4-phenylpiperidine structural fragment found in the central analgesic agent meperidine and its derivatives (see Chapter 7). The former compound may well have been discovered in the course of further SAR studies on the opiate [20]. An unusual synthesis of haloperidol starts with the product (18-1) from Friedel-Crafts acylation of 4-fluorobenzene with succinic anhydride. Successive protection of the... 

In ordinary doses, meperidine exerts inappreciable effects on respiration and circulation. In large doses, it interferes with the facilitatory function of the pneumotaxic center and the vagal afferent impulses, thereby reducing the rate and depth of respiration. With still higher doses, meperidine produces an irregular respiratory rhythm and ultimately induces apnea. It causes relaxation of the ureter, gall bladder, and bronchi. This action is partly a direct one on the smooth muscle of these structures and, in part, a result of its anticholinergic activity. It does not affect the size of the pupil or alter the tonus of the uterus. 

Although morphine and meperidine are quite similar in their clinical effects, they are not that similar in chemical composition. The important chemical determinant of an opioid analgesic, however, is not its structural resemblance to morphine, but its ability to bind with and activate an opioid receptor. 

Another example of the largest common substructure search is shown in Fig. 6. Although they differ greatly in structure from one another, morphine, meperidine, and methadone exhibit similar pharmacological activities (analgesic properties). By the search with level (4) expression, two connected graphs are... 

The gold standard of opiate pain relievers is morphine. It was one of the first compounds extracted, isolated, and purified from the opium poppy, and it continues to be one of the most widely used pain relievers today. Morphine and other opiate drugs such as heroin, codeine, oxycodone, and hydrocodone have very similar chemical structures (Figure 3.2). However, other opiates such as fentanyl and meperidine (Demerol) have a slightly different structure (Figure 3.3). 

Meperidine [me PER i deen] is a synthetic opioid with a structure... 

Fig. 11.14 Structures of the phenylpiperidine, meperidine reverse meperidine (MPPP), MPTP, and MPP+.

Com- pound Ri Structure Ri R) R. Name (If Any) Analgesic Activity (Meperidine ° t)... 

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