Pethidine

Meperidine (isonipecaine, Demerol , and Dolantin ) is the methyl ester of methyl-4-phenylpi-peridine-4 carboxylic acid. It is used in the form of its soluble hydrochloride. The piperidine nucleus is also present in many alkaloids, such as atropine or lobeline, which are not analgesics, as well as in morphine. 

Meperidine shows certain relationships to both morphine and atropine in its action. Similar to morphine, it exerts a generalized depression of the CNS but, in ordinary doses, does not affect the cough reflex. Similar to morphine, it induces euphoria, and its continued use leads to tolerance and addiction. However, its euphoric and sedative effects are less than that of morphine addiction due to meperidine is more serious than that due to morphine. Meperidine is an effective analgesic, 

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. 

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Perylene-3,4,9,10-bis(dicarbonamide) electrical conductivity, 1, 358 Perylene hexafluoroarsenate conductors, 1, 355 Perylene vat dyes, 1, 336-337 Pestalotin synthesis, 3, 841 Pethidine... 

A useful review of information on pethidine has been published by Batterman and Himmelsbach, and an admirable summary of information on synthetic analgesics has been provided by Morrison and Rinderknecht. °( >... 

Pereirine pereiro bark, 735, 736 Perlolidine, 749, 750 Perloline, 749, 751 Persea gratissima, 320, 781 Pethidine, 265... 

A not uncommon side effect observed with morphine and some of the other narcotic analgesics is constipation due to decreased motility of the gastrointestinal tract. It proved possible to so modify pethidine as to retain the side effect at the expense of analgesic activity. Relief of diarrhea, it will be realized, is a far from trivial indication. Alkylation of the anion from diphenylacetonitrile (95) with ethylene dibromide gives the intermediate, 96. Alkylation of normeperidine (81) with that halide... 

In an effort to more closely mimic the aromatic substitution pattern found in morphine (see A) the pethidine analog containing the m-hydroxy group was prepared as well. Thus, in a synthesis analogous to that used to prepare the parent compound, double alkylation of m-methoxyphenylacetonitrile with the chloroamine. 

An analog of the above "reversed" pethidine, alphaprodine (114), has found application as an analgesic in the clinic. 

Pentazocine j, 297 2 325 Pentobarbital 1, 268 Pentomone 3, 2T8 PentoxphylTine 466 Pentyl enetetrazole 281 Perazine 1, 381 Pergolide 249 Perlapine 425 Perphenazine 1, 383 Pethidine 1, 300 Phenacaine 19 Phenacemide 1, 95 Phenacetemide Phenacetin 111... 

Common Name Isonipecaine hydrochloride pethidine hydrochloride Structural Formula 3... 

Alfentanil, codein, dihydromorphine, etor-phine, fentanyl, heroin, hydromorphone, levo-methadone, morphine, oxycodone, pethidine, piritramide, remifentanil, sufentanil, tilidine, tramadol Buprenorphine, pentazocine Naloxone, naltrexone... 

Cj H7N 140-29-4) see Azatadine Dicycloverine Disopyramide Ethoheptazine Isoaminile Levocabastine Mephenytoin Methylphenidate Methylphenobarbital Milnacipran hydrochloride Oxeladin Pentapiperide Pentoxyverine Pethidine Phenglutarimide Pheniramine Phenobarbital Tolazoline Triamterene Valethamate bromide 1 -benzy l-4-cyanopiperidine (C]3H 9N2 62778-37-4) see Ketanserin... 

C4H8CI2O 111-44-4) see Benzethonium chloride Oxeladin Risperidone /V,/V-bis(2-chloroethyl)-N-methylamine (C5H11CI2N 51-75-2) see Ketobemidone Pethidine... 

Recently much interest has centred on a very specific toxin for DA neurons. This is 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). It was discovered when a student, who was addicted to pethidine, tried to manufacture l-methyl-4-phenyl-4-propionoxy-piperidine (MPPP) but took a short-cut in synthesis and produced MPTP. When he administered this to himself he developed Parkinsonism. MPTP destroys DA neurons. Again this process depends on the neuronal uptake mechanism, since MPTP itself is not the active material. It needs to be deaminated to MPP+ which is then taken up by DA nerve terminals. 

Synthetic agonist Morphine Codeine Fentanyl Pethidine DSTBULET DPDPE U50488H Pentazocine Oxycodone ... 

Szeto HH, Inturrisi CE, Houde R, Saal S, Cheigh J and Reidenberg M (1977). Accumulation of norperidine, an active metabolite of meperidine [pethidine], in patients with renal failure or cancer. Annals of Internal Medicine, 86, 738-741. 

Reference compounds. Dipipanone Rf 66, pethidine Rf 37, desipramine Rf 20, codeine Rf 06. 

FIGURE 1.32 Extraction-time profiles for promethazine (A), methadone (B), amphetamine (C), pethidine (D), and haloperidol (E) in 1 mL sample volume with 0, 5, and 50% methanol added to plasma sample.155 (Reproduced with permission from the Royal Society of Chemistry.)... 

Morphine Diamorphine Codeine Pethidine Fentanyl Alfentanil Remifentanil... 

Mepivacine, bupivacine, doxapram, quinine, quinidine, atenolol, metoprolol, propranolol, pethidine, methadone (5)-N-(3,5-dinitro-benzoyl) tyrosine Acetonitrile—ammo 208 nium acetate (60 40)... 

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