Basic information Safety Supplier Related

MEPERIDINE HYDROCHLORIDE

Basic information Safety Supplier Related

MEPERIDINE HYDROCHLORIDE Basic information

Product Name:
MEPERIDINE HYDROCHLORIDE
Synonyms:
  • 1-METHYL-4-PHENYLPIPERIDINE-4-CARBOXYLIC ACID ETHYL ESTER HYDROCHLORIDE
  • MEPERIDINE HYDROCHLORIDE
  • 1-methyl-4-carbethoxy-4-phenylpiperidinehydrochloride
  • 1-methyl-4-phenyl-4-carboethoxypiperidinehydrochloride
  • 1-methyl-4-phenylisonipecoticacidethylesterhydrochloride
  • 4-piperidinecarboxylicacid,1-methyl-4-phenyl-,ethylester,hydrochloride
  • algil
  • alodan(gerot)
CAS:
50-13-5
MF:
C15H22ClNO2
MW:
283.79
EINECS:
200-013-3
Product Categories:
  • Aromatics
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Neurochemicals
  • Pharmaceuticals
Mol File:
50-13-5.mol
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MEPERIDINE HYDROCHLORIDE Chemical Properties

Melting point:
186-189°
Boiling point:
282°C (rough estimate)
Density 
1.0858 (rough estimate)
refractive index 
1.5200 (estimate)
Flash point:
11 °C
storage temp. 
2-8°C
solubility 
Very soluble in water, freely soluble in alcohol.
CAS DataBase Reference
50-13-5
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Safety Information

Hazard Codes 
T,F
Risk Statements 
25-39/23/24/25-23/24/25-11
Safety Statements 
26-36/37/39-45-36/37-16-7
RIDADR 
1544
WGK Germany 
3
RTECS 
NS5950000
HazardClass 
6.1(b)
PackingGroup 
III
HS Code 
2933330000
Toxicity
LD50 orally in rats: 170 mg/kg (Barlow, Lewis)
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MEPERIDINE HYDROCHLORIDE Usage And Synthesis

Chemical Properties

White or almost white, crystalline powder.

Originator

Dolosal,Specia,France,1943

Uses

Analgesic; sedative; anesthetic. Controlled substance (opiate).

Definition

An addictive drug, use by prescription only.

Manufacturing Process

80 parts of finely pulverized sodium amide are added in portions each of about ? of the entire quantity, while stirring and cooling in a suitable manner, to a mixture of 756 parts of methyl-di(β-chloroethyl)-amine (prepared from di-ethanol-methylamine by means of thionyl chloride), 117 parts of benzyl cyanide and 600 parts of toluene. The reaction sets in at once at room temperature. The temperature is maintained between 30° and 40°C; when self-heating no longer occurs a further portion of the sodium amide is introduced. During the reaction heat is liberated and gaseous ammonia escapes.
The mixture is then slowly heated to the boiling point of toluene and kept boiling for one hour under reflux. After the mixture has been allowed to cool the sodium chloride which precipitates is separated by extraction with water. The solution of toluene is then extracted with dilute hydrochloric acid. From the hydrochloric acid extract the basic substance is separated in the form of an oil by means of caustic soda solution and is introduced into ether. The ethereal solution is dried with the aid of potassium carbonate and then distilled.
Under a pressure of 4.5 ml the 1-methyl-4-phenyl-piperidine-4-carboxylic acid nitrile passes over at a temperature of about 148°C in the form of a colorless oil; under a pressure of 6 ml it passes over at about 158°C. After having been allowed to cool the distillate solidifies completely to form a crystalline mass. Its solidification point is at 53°C; the yield amounts to about 135 parts, that is, about 2/3 of the theoretical yield. When recrystallized from isopropyl alcohol the hydrochloride of the nitrile forms colorless crystals, readily soluble in water and melting at 221° to 222°C.
The nitrile may best be saponified with methyl alcoholic potash while heating to 190° to 200°C with application of pressure. After the methyl alcohol has evaporated the salt is introduced into water and by the addition of dilute mineral acid until the alkaline reaction to phenolphthalein has just disappeared, the amphoteric 1-methyl-4-phenyl-piperidine-4-carboxylic acid is precipitated while hot in the form of a colorless, coarsely crystalline powder. When dried on the water bath the acid still contains 1 mol of crystal water which is lost only at a raised temperature. The acid melts at 299°C. Reaction with ethanol yields the ester melting at 30°C and subsequent reaction with HCl gives the hydrochloride melting at 187° to 188°C.

brand name

Demerol (Hospira); Demerol (Sanofi Aventis).

Therapeutic Function

Narcotic analgesic

Biochem/physiol Actions

Phenylpiperidine analgesic; sedative; μ opioid receptor agonist with greater κ opioid receptor agonist activity than morphine.

Clinical Use

Meperidine is a μ agonist with approximately one-tenth the potency of morphine after intramuscular dose. Meperidine produces the analgesia, respiratory depression, and euphoria caused by other μ opioid agonists, but it causes less constipation and does not inhibit cough. When given orally, meperidine has 40 to 60% bioavailability because of significant first-pass metabolism. Because of the limited bioavailability, it is one-third as potent after an oral dose compared to a parenteral dose.
Meperidine has received extensive use in obstetrics because of its rapid onset and short duration of action. When it is given intravenously in small (25-mg) doses during delivery, the respiratory depression in the newborn child is minimized. Meperidine is used as an analgesic in a variety of nonobstetric anesthetic procedures. Meperidine is extensively metabolized in the liver, with only 5% of the drug being excreted unchanged. Prolonged dosage of meperidine may cause an accumulation of the metabolite normeperidine. Normeperidine has only weak analgesic activity, but it causes CNS excitation and can initiate grand mal seizures. It is recommended that meperidine be discontinued in any patient who exhibits signs of CNS excitation.
Meperidine has a strong adverse reaction when given to patients receiving a monoamine oxidase inhibitor. This drug interaction has been seen recently in patients with Parkinson's disease taking the monoamine oxidase–selective inhibitor selegiline (Eldepryl).
The elimination half-life of meperidine is 3 to 4 hours, and it can double in patients with liver disease. Acidification of the urine will cause enhanced clearance of meperidine, but there is a lesser effect on the clearance of the toxic metabolite normeperidine.

Safety Profile

Poison by ingestion, subcutaneous, intravenous, and intraperitoneal routes. Moderately toxic by parenteral route. Experimental teratogenic effects. Mutation data reported. An analgesic. When heated to decomposition it emits very toxic fumes of HCl and NOx.

Veterinary Drugs and Treatments

Although no product is licensed in the United States for veterinary use, this agent has been used as an analgesic in several different species. It has been used as sedative/analgesic in small animals for both post-operative pain and for medical conditions such as acute pancreatitis and thermal burns, but usually other opiates are preferred as the drug has a short analgesic duration of activity and can cause significant histamine release. It is occasionally used in equine medicine in the treatment of colic and in other large animal species for pain control.

Drug interactions

Potentially hazardous interactions with other drugs
Analgesics: possible opioid withdrawal with buprenorphine and pentazocine.
Anti-arrhythmics: delayed absorption of mexiletine.
Antidepressants: possible CNS excitation or depression with MAOIs and moclobemide - avoid; possibly increased serotonergic effects with duloxetine; increased sedative effects with tricyclics.
Antiepileptics: possible increased risk of pethidine toxicity with fosphenytoin and phenytoin.
Antihistamines: increased sedative effects with sedating antihistamines.
Antipsychotics: enhanced sedative and hypotensive effect.
Antivirals: concentration reduced by ritonavir but concentration of toxic pethidine metabolite increased - avoid.
Dopaminergics: risk of CNS toxicity with rasagiline - avoid; hyperpyrexia and CNS toxicity reported with selegiline - avoid.
Nalmefene: avoid concomitant use.
Sodium oxybate: enhanced effect of sodium oxybate - avoid.

Metabolism

Pethidine is metabolised in the liver by hydrolysis to pethidinic acid or by demethylation to norpethidine (active metabolite) and hydrolysis to norpethidinic acid, followed by conjugation with glucuronic acid.
Norpethidine is pharmacologically active and its accumulation may result in toxicity. Pethidine has a half-life of about 3-6 hours; norpethidine is eliminated more slowly, with a half-life reported to be up to about 20 hours.

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