Absorption, Distribution and Excretion
...Mephentermine.../is/ readily absorbed from the digestive tract. .../It/may be absorbed by the nasal mucosa, but the degree of absorption may vary. Most of the drug is excreted in the urine within 24 hours. Mephentermine is reabsorbed in the renal tubules. The drug and its metabolites are excreted more quickly in acidic urine. Metabolism/Metabolites Hepatic metabolism via N-demethylation and para-hydroxylation. Mephentermine is metabolized in the liver via N-demethylation and subsequent para-hydroxylation to normephentermine and para-hydroxynormephentermine. /Sulfate/ In vitro, mephentermine can be metabolized by rabbit liver microsomes to phentermine (II), N-hydroxymephentermine (III), and N-hydroxyphentermine. Metabolites (II) and (III), as well as unchanged phentermine, were found in the urine of individuals who received a single dose of mephentermine sulfate.
Metabamine (MP), phentermine (Ph), p-hydroxy-MP, p-hydroxy-Ph, N-hydroxy-MP, and N-hydroxy-Ph metabolites were identified by glucose and glucose mass spectrometry after incubation with rat liver microsomes and cytoplasm. Metabolite identification revealed the following novel metabolic pathways for MP: an NADPH-dependent microsomal pathway, where MP generates p-hydroxy-MP; p-hydroxy-MP generates p-hydroxy-Ph; and an NADH-dependent microsomal pathway, where N-hydroxy-Ph generates Ph.
This article describes the urinary excretion of mephentermine (I) and its major metabolite phentermine (II) in human volunteers over several days after oral administration. Total drug excretion within 54 hours ranged from 57% to 83%. Administration of acetazolamide shortly after administration of I resulted in a decrease in the excretion of both I and II within one day. Administration of furosemide only produced urinary dilution within 2–4 hours after administration.
Biological half-life
17–18 hours.
17–18 hours

Interactions
In anesthetized dogs, risperidone enhances the pressor response when administered after mephentermine. In cats and mice, repeated injections of mephentermine and dextromethorphan resulted in rapid tolerance to the blood pressure response. Tolerance to these substances cross-links and with phenethylamine, but not with tyramine, due to different sites of action. The site of norepinephrine release by tyramine may differ from that of dextromethorphan, mephentermine, and phenethylamine, but these two storage sites may be functionally related. At a non-excitatory dose (1 mg/kg), intravenous co-administration of mephentermine with 1 mg/kg rivaroxaban in dogs and rabbits produced an acute adrenocorticotropic hormone (AER) response. Rabbits pre-injected with α-methyl-m-tyrosine (100 mg/kg) appeared normal, exhibited persistent EEG activation in response to external stimuli, and developed AER (acute respiratory distress) under the combined drug administration. Imipramine hydrochloride at 5 mg/kg can inhibit AER, while desmethylimipramine cannot block or alter its process. Scopolamine hydrobromide at 1–5 mg/kg can only inhibit the EEG activation of AER. Pretreatment with isoprohydrine (100 mg/kg) prolongs the stimulation effect of the drug combination but does not change the effect of mephentermine alone. Pretreatment of rabbits with rixepine reduces or eliminates CNS excitation induced by mephentermine, but threshold doses of methamphetamine (1–5 mg/kg) can still induce CNS excitation. The combined use of rixepine (1 mg/kg) and mephentermine (1 mg/kg), rather than rixepine or mephentermine alone, alters the EEG activation pattern in curare rabbits and eliminates the single-shock response in the midbrain reticular formation within approximately 28 minutes. Chlorpromazine (5 mg/kg) can block the combined effect of these drugs. Rifampin apparently enhances the indirect effects of mephentermine, and the presence of brain biogenic amines is a necessary condition for this stimulation. For more complete data on interactions with mephentermine (27 in total), please visit the HSDB records page.

[1]. Mephentermine Misuse: An Impending Crisis among Sportspersons [published online ahead of print, 2021 Jun 14]. J Psychoactive Drugs. 2021;1-3.

Mephentermine belongs to the amphetamine class of drugs. It is a sympathomimetic drug that primarily works indirectly through its action on adrenergic receptors. For example, it can be used to maintain blood pressure in hypotensive states after spinal anesthesia. Although the central nervous system stimulant effect of mephentermine is much less than that of amphetamines, its use can still lead to amphetamine-like dependence. (From Martindale Pharmacopoeia, 30th edition, p. 1248) It is a sympathomimetic drug specific to α1-adrenergic receptors. It is used to maintain blood pressure in hypotensive states, such as after spinal anesthesia. See also: Mephentermine sulfate dihydrate (note moved to). Indications: Used to maintain blood pressure in hypotensive states. Mechanism of Action: Mephentermine is an α-adrenergic receptor agonist, but it can also act indirectly by releasing endogenous norepinephrine. Cardiac output, as well as systolic and diastolic blood pressure, is typically increased. Heart rate changes vary depending on the degree of vagal tone. Sometimes, its net vasoconstrictive effect may be vasodilation. High doses may inhibit the myocardium or produce central nervous system (CNS) effects.
Mefphenidamine is a sympathomimetic drug with both direct and indirect mechanisms of action; it shares many similarities with ephedrine. After intramuscular injection, it has a rapid onset of action (within 5 to 15 minutes) and its effects can last for several hours.
Because this drug releases norepinephrine, it can enhance myocardial contractility, generally increasing cardiac output as well as systolic and diastolic blood pressure. Heart rate changes vary depending on vagal tone.
Therapeutic Uses

Adrenergic α-receptor agonist; adrenergic drug; sympathomimetic drug; vasoconstrictor
Mefphenidamine…is used to prevent hypotension, which is common after spinal anesthesia.
It is not recommended as a routine treatment for shock (especially hypovolemic shock), but can be used as a temporary medication during preparation for resuscitation and other interventions. /Sulfate/
...The free base can be used topically as a mydriatic.
For more complete data on the therapeutic uses of mephentermine (9 types), please visit the HSDB record page.

---

Drug Warnings
Mephentermine may cause arrhythmias, including premature contractions, atrioventricular block, and hypertension. Patients with heart disease or taking other medications that may increase cardiac excitability (such as cyclopropane or halogenated hydrocarbon general anesthetics) are most susceptible to arrhythmias. /Mephentermine Sulfate/
The central nervous system stimulant effect of mephentermine may cause tension, anxiety, seizures, or tachycardia. Overdose of this drug can cause visual hallucinations of colored geometric figures, paranoid psychosis, and euphoria. Drowsiness, crying, incoherent speech, weakness, numbness, and tingling in the extremities have been reported. Central nervous system adverse reactions disappear rapidly after discontinuation of the drug. Mephentermine Sulfate
Adverse reactions are very rare because it is currently used in the free base form.
Mefphenidene may increase uterine contractions, especially in late pregnancy; therefore, it should not be used in pregnant women unless the potential benefits outweigh the possible risks. Mefphenidene Sulfate
For more complete data on drug warnings for mefphenidene (10 in total), please visit the HSDB records page.

---

Pharmacodynamics
Mefphenidene is a sympathomimetic drug that works primarily through indirect action on adrenergic receptors. It is used to maintain blood pressure in hypotensive states, such as after spinal anesthesia. Although the central nervous system stimulant effect of mefphenidene is far less than that of amphetamines, its use can still lead to amphetamine-like dependence. (Excerpt from Martindale Pharmacopeia, 30th edition, page 1248)

C11H17N.1/2H2SO4

212.30

424.24

1212-72-2

Mephentermine hydrochloride;3978-34-5

3677

LIQUID

229.4ºC at 760mmHg

< 25 °C
YELLOW CRYSTALS; MP: 155-156 °C /PICRATE/
< 25 °C

90ºC

1.94E-20mmHg at 25°C

5.664

1

1

3

12

123

0

CC(C)(CC1=CC=CC=C1)NC.CC(C)(CC1=CC=CC=C1)NC.OS(=O)(=O)O

RXQCGGRTAILOIN-UHFFFAOYSA-N

InChI=1S/C11H17N/c1-11(2,12-3)9-10-7-5-4-6-8-10/h4-8,12H,9H2,1-3H3

N,2-dimethyl-1-phenylpropan-2-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)