(Hive Bee)
10-08-02 13:10
No 366157
      Anileridine, a pethidine analog.
(Rated as: excellent)

Anileridine is an analog of pethidine, where the methyl group on the nitrogen is replaced by a p-aminophenethyl group.  Ehyl 1-(4-aminophenethyl)-4-phenylisonipecotate is prepared by reacting ethyl 4-phenylisonipecotate and p-aminophenethylchloride.HCl in alcohol with sodium bicarbonate.  The freebase can be precipitated from ether solution by gassing it with HCl.  The dihydrochloride can be purified by crystallization from methanol - ether, which can be further purified by crystallization from methanol, M.P.: 280 - 287 C.

The N-acetyl monohydrochloride can be prepared by treatment of the free base (M.P.: 83 C) with acetic anhydride - acetic acid at 90 - 100 C. (M.P. of the N-acetyl monohydrochloride = 264 - 265 C).

Anileridine, is a potent analgesic with high oral activity and relative mild side reactions.  Mild anti-acetylcholine and antihistaminic activity has been observed in both isolated organs and in intact animals.  In animals, the compound approaches morphine in analgesic potency and is several times more active than pethidine (ethyl 1-methyl-4-phenylisonipecotate).  Unlike pethidine, it is a good antitussive agent against experimental cough in guinea pigs and dogs.  The side reactions in such animals such as general depression and sedation, depression of respiratory and lowering of blood pressure, are considerably milder than those produced by morphine, and somewhat milder than those of pethidine.  Anileridine does not produce nausea, vomiting or constipation in animals.
The acute oral and subcutaneous toxicity of the compound, as measured in mice, is of the same order as pethidine, but it is somewhat more toxic on intravenous administration.
After subcutaneous injection into rats, a bound form, probably the N-acetyl derivative, was found in the tissues.  The N-acetyl derivative has analgesic activity of the same order as the parent compound when tested in rats.
Preliminary results in man by oral and parenteral administration indicate an analgesic potency at least twice that of pethidine.

EDIT: Ref.: JACS (1956) vol 78 p 2342 - 2343

The more systematic name of anileridine is 1-para-aminophenethyl-4-phenylpiperidine-4-carboxylic acid ethyl esther.  Dose: 25 - 50 mg, every 6 hours.

For more synthetic details, cfr. US patent 2,966,490
(Chief Bee)
10-08-02 14:33
No 366197
      More Anileridine Data  Bookmark   

From "New and non-official drugs 1963":

Anileridine Hydrochloride:

The drug is rapidly absorbed from the gastrointestinal tract and provides analgesia for 2-4 h. The usual oral dosage is 25 mg every 6 h, if necessary. A dosage of up to 50 mg, or more frequent doses, may be desirable for more severe pain.

Anileridine Phosphate:

Anileridine Phosphate is a synthetic analgesic compound closely related in chemical structure and pharmacological action to meperidine hydrochloride. Its analgesic potency lies between that of meperidine and morphine; on the basis of its ability to relieve pain in man, anileridine appears to be about two and onehalf times as potent as equal amounts of meperidine and approximately one-quarter as potent as the same weight of morphine. Iike meperidine, anileridine exerts mild antihistaminic and spasmolytic effects, but it does not produce the constipating effect of the opiates. In the usual range of analgesic doses, sedative and direct hypnotic effects are minimal, being about the same as with meperidine but somewhat less than with morphine. Anileridine also exerts an antitussive effect, but this has not been evaluated clinically. It is similar to meperidine in that it does not produce as much dizziness, nausea and vomiting as morphine in patients confined to bed. The incidence of such effects is probably increased by ambulation as with all other narcotic analgesics, thus limiting its use in ambulatory patients. In equianalgesic doses the degree of respiratory depressant effect of anileridine is not significantly different from that of meperidine, but it is apparently of shorter duration. Circulatory depression is less than with meperidine. As with all narcotics, anileridine potentiates the action of the ultrashortacting barbiturates and other central nervous system depressants. The drug is promptly absorbed after parenteral administration, and peak plasma levels are reached within 1 hour. Its duration of action is slightly less than that of meperidine; analgesic effects persist for about 0.5 to 1 hour after intravenous administration, 1 to 2 hours after intramuscular administration and 3 to 4 hours after subcutaneous injection. Animal experiments indicate that the kidney and the liver are the principal sites of degradation and excretion.

Anileridine phosphate is useful for the relief of moderate to severe pain. It may be used as an analgesic adjunct in general anesthesia in the same manner as meperidine to reduce the amount of anesthetic needed. to facilitate relaxation and to reduce laryngospasm. The drug is also useful postoperatively for the relief of wound pain. Anileridine has also been employed for obstetric analgesia, both alone or in combination with scopolamine or barbiturates. The results have been satisfactory, as a rule, for the mother, but some degree of fetal respiratory depression has been observed. There are also indications that the drug may slow labor. In general, anileridine appears to have the same usefulness and the same limitations as meperidine and is considered a satisfactory substitute for meperidine in all conditions in which that drug may be indicated. It will not relieve the most severe pain as effectively as morphine.

Anileridine has an addiction liability equivalent to that of morphine and is subject to the federal narcotic law. It suppresses morphine abstinence completely, whereas meperidine does not; in this sense, it has an addiction liability greater than that of meperidine. On the other hand, the dose of anileridine required to sustain addiction is about the same as that of meperidine, even though two and a half times as much meperidine as anileridine is needed to produce equal analgesic effects.

Respiratory depression and, to a somewhat lesser degree, circulatory depression are the chief hazards attending the use of anileridine. These effects are particularly prone to occur in elderly patients or in patients in whom the drug is administered too fast by the intravenous route. Special caution should be observed when the drug is used in conjunction with other narcotics, sedatives or anesthetics, since these agents enhance respiratory depression. Should significant respiratory depression occur, this can be reversed by administration of nalorphine. Side effects with anileridine are no more troublesome than with meperidine and include occasional nausea and vomiting, dizziness, perspiration, feeling of warmth, xerostomia, restlessness, nervousness and excitement. Except in high concentration, parenteral injection causes little tissue irritation.

Dosage: Anileridine phosphate is administered by subcutaneous, intramuscular or intravenous injection. Dosage varies according to severity of pain and response of the patient. For single subcutaneous or intramuscular injection in adults, the usual initial dose is 25 to 50 mg. This may be repeated at intervals of 4 to 6 hours as required. The usual dose for obstetric analgesia is 50 mg. repeated in 3 to 4 hours. For intravenous use in support of anesthesia, the drug should be well diluted and administered slowly. For adults, 50 to 100 mg. is diluted with 500 cc, of 5 per cent dextrose in water for injection. Enough of this diluted solution to provide 5 to 10 mg. is then infused slowly. Analgesia is maintained by slow intravenous drip at a rate adjusted to provide about 0.6 mg. per minute, depending on individual need and response. Direct intravenous injection of the concentrated commercial solution should not be attempted except under grave emergency situations when time or facilities do not permit dilution of the drug. If used under these conditions, the rate of injection should be extremely slow, so that the injection takes at least several minutes. It should be borne in mind that the sudden intravenous injection of an amount greater than 10 mg may cause apnea.
(Chief Bee)
01-13-03 14:28
No 397884
      Anileridine synthesis  Bookmark   

Post 397794 (Aurelius: "US pat 2966490 synth of Anileridine", General Discourse)
(Hive Addict)
01-13-03 16:00
No 397899
      Rhodium  Bookmark   

Damn you're fast.  aurelius was going to link that.