Absorption, Distribution and Excretion
The effect starts 1-2 min after IV injection, 10 min after IM injection, 5-20 min after subcutaneous injection.
METARAMINOL IS ABSORBED AFTER ORAL ADMINISTRATION.
METARAMINOL WAS TAKEN UP BY THE RABBIT HEART IN MEASURABLE QUANTITIES FOR AT LEAST 8 DAYS FOLLOWING A SINGLE IV INJECTION. IT WAS EXTENSIVELY DISTRIBUTED IN HEART, LUNGS, LIVER, KIDNEYS, & SKELETAL MUSCLE & POORLY IN THE SPLEEN, BRAIN, FAT, & STOMACH.
EXCEPT FOR THE BRAIN, PERIPHERALLY ADMIN METARAMINOL WAS WELL DISTRIBUTED IN RATS. ORGANS WITH A LARGE POPULATION OF NOREPINEPHIRINE (NE) STORAGE VESICLES SUCH AS THE HEART, SPLEEN, & ADRENAL, TOOK UP RELATIVELY LARGE AMT & RETAINED IT LONGER THAN LIVER, LUNG & KIDNEY.
METARAMINOL IS ABSORBED AFTER ORAL ADMIN; HOWEVER, FOR EQUAL EFFECTS, ORAL DOSES MUST BE 5 OR 6 TIMES GREATER THAN DOSES GIVEN IM OR IV. THE PRESSOR EFFECT OF AN IM DOSE OF 5 MG LASTS FOR ABOUT 1.5 HOURS.

---

Metabolism / Metabolites
Hepatic
THE FACT THAT METARAMINOL, 1-(M-HYDROXYNOREPHEDRINE), REMAINED UNCHANGED & BOUND TO TISSUES FOR 1-2 WK AFTER INGESTION PROMPTED IN VITRO STUDIES, WHICH SHOWED THAT THE DRUG RESISTS BIOTRANSFORMATION BY LIVER ENZYMES WHICH METABOLIZE STRUCTURALLY RELATED COMPOUNDS. /MAMMAL SPECIES NOT LISTED IN SOURCE/

Protein Binding
Approximately 45%

---

Interactions
MAO INHIBITORS...HAVE THE POTENTIAL FOR DRUG INTERACTION WITH METARAMINOL THROUGH INHIBITION OF OXIDATIVE DEAMINATION OF SYMPATHOMIMETIC AMINES. THE RESULT MAY BE AN INCREASED TISSUE STORE OF NOREPINEPHRINE, WHICH WILL PRODUCE A HEIGHTENED HYPERTENSIVE RESPONSE SECONDARY TO THE INDIRECT ACTIONS OF METARAMINOL. /BITARTRATE/
GUANETHIDINE, RESERPINE, & METHYLDOPA AFFECT POSTGANGLIONIC NERVE ACTIVITY, EITHER BY DECREASING NOREPINEPHRINE STORES OR BY EFFECTING ITS RELEASE. THEREFORE, THESE DRUGS WILL INTERFERE WITH THE INDIRECT NOREPINEPHRINE-RELEASING ACTIONS OF METARAMINOL & MAY LIMIT ITS EFFICACY. /BITARTRATE/
CARDIAC OUTPUT INCREASES STRIKINGLY WHEN SLOWING OF THE HEART IS PREVENTED BY ATROPINE.
THE ANTIBACTERIAL ACTION OF FURAZOLIDONE IS ACCOMPANIED BY PROGRESSIVE & GENERALIZED INHIBITION OF MONOAMINE OXIDASE & THE CONCURRENT OR SUBSEQUENT ADMIN OF /METARAMINOL/...COULD RESULT IN A HYPERTENSIVE CRISIS. /BITARTRATE/
For more Interactions (Complete) data for METARAMINOL (20 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LD50 Rat oral 240 mg/kg
LD50 Rat ip 41 mg/kg
LD50 Rat sc 117 mg/kg
LD50 Mouse oral 99 mg/kg
For more Non-Human Toxicity Values (Complete) data for METARAMINOL (6 total), please visit the HSDB record page.

Metaraminol is a member of the class of phenylethanolamines that is 2-amino-1-phenylethanol substituted by a methyl group at position 2 and a phenolic hydroxy group at position 1. A sympathomimetic agent , it is used in the treatment of hypotension. It has a role as an alpha-adrenergic agonist, a sympathomimetic agent and a vasoconstrictor agent.
An adrenergic agonist that acts predominantly at alpha adrenergic receptors and also stimulates the release of norepinephrine. It has been used primarily as a vasoconstrictor in the treatment of hypotension.
A sympathomimetic agent that acts predominantly at alpha-1 adrenergic receptors. It has been used primarily as a vasoconstrictor in the treatment of HYPOTENSION.

---

Drug Indication
For the treatment and prevention of hypotension due to hemorrhage, spinal anesthesia, and shock associated with brain damage

---

Mechanism of Action
Metaraminol acts through peripheral vasoconstriction by acting as a pure alpha-1 adrenergic receptor agonist, consequently increasing systemic blood pressure (both systolic & diastolic). Its effect is thought to be associated with the inhibition of adenyl cyclase which leads to an inhibition of the production of cAMP. Another effect of Metaraminol is that it releases norepinephrine from its storage sites indirectly.
BY DIRECT ACTION ON ALPHA ADRENERGIC RECEPTORS & INDIRECT ACTION THROUGH THE RELEASE OF NOREPINEPHRINE FROM STORAGE SITES...PRODUCES VASOCONSTRICTION, INCREASED PERIPHERAL VASCULAR RESISTANCE, & A RESULTANT INCREASED BLOOD PRESSURE. REFLEX BRADYCARDIA USUALLY OCCURS &...RENAL & CEREBRAL BLOOD FLOW DECREASES. /BITARTRATE/
CARDIAC INOTROPY INCREASES, BUT LESS SO THAN WITH NOREPINEPHRINE & CARDIAC OUTPUT REMAINS UNCHANGED OR MAY SLIGHLY DECREASE IF BRADYCARDIA OCCURS. SOME BETA ADRENERGIC MEDIATED VASODILATION OCCURS WITH METARAMINOL, BUT ALPHA EFFECTS PREDOMINATE. /BITARTRATE/
FOLLOWING IV ADMIN OF 1.5 MG/KG TO RABBITS, THERE WAS A POSITIVE CORRELATION BETWEEN PLASMA DRUG LEVEL & ITS VASOPRESSOR EFFECT. DRUG IS APPARENTLY DIRECT-ACTING SYMPATHOMIMETIC AMINE & ITS ACTION IS PROBABLY TERMINATED BY ITS DILUTION IN BODY FLUIDS & TISSUE UPTAKE.

---

Therapeutic Uses
Adrenergic alpha-Agonists; Adrenergic Agents; Sympathomimetics; Vasoconstrictor Agents
MEDICATION (VET): /USED/ IN HYPOTENSIVE STATES IN DOGS AS MAY OCCUR IN ENDOTOXIC SHOCK OR BARBITURATE ANESTHESIA. /IT/ HAS BEEN USED WITH PHENYLEPHRINE OR AMPHETAMINE. PROBABLY INDICATED IN SHOCK ASSOCIATED WITH MYOCARDIAL INFARCTION.
...USED...IN CERTAIN ACUTE HYPOTENSIVE CONDITIONS SUCH AS ANAPHYLACTIC SHOCK (AFTER INITIAL MANAGEMENT WITH EPINEPHRINE) OR SHOCK SECONDARY TO MYOCARDIAL INFARCTION, TRAUMA, SEPTICEMIA, GRAM-NEGATIVE BACTERIAL ENDOTOXINS, & ADVERSE DRUG REACTIONS. /BITARTRATE/
... IS USED ALMOST EXCLUSIVELY FOR TREATMENT OF HYPOTENSIVE STATES. IT HAS BOTH DIRECT & INDIRECT ACTION & ITS OVERALL EFFECTS ARE SIMILAR TO THOSE OF NOREPINEPHRINE, BUT IT IS MUCH LESS POTENT & HAS A MORE PROLONGED ACTION. IT LACKS CNS STIMULANT EFFECTS.
For more Therapeutic Uses (Complete) data for METARAMINOL (12 total), please visit the HSDB record page.

---

Drug Warnings
VET: CONTINUED USE MAY DEPLETE NOREPINEPHRINE STORES.
IT IS NOT RECOMMENDED IN HYPOVOLEMIC SHOCK. /BITARTRATE/
...METARAMINOL CAN CAUSE SHOCK WHEN GIVEN BY PROLONGED INFUSION & SOME AUTHORITIES ARE RELUCTANT TO GIVE METARAMINOL...IN ANY KIND OF SHOCK OTHER THAN ANAPHYLAXIS. METARAMINOL CAN CAUSE A SLOUGH IF EXTRAVASATED. /BITARTRATE/
SUBCUTANEOUS INJECTIONS SHOULD BE AVOIDED SINCE TISSUE SLOUGHING MAY OCCUR.
For more Drug Warnings (Complete) data for METARAMINOL (14 total), please visit the HSDB record page.

---

Pharmacodynamics
Metaraminol is a potent sympathomimetic amine that increases both systolic and diastolic blood pressure. Metaraminol is indicated for prevention and treatment of the acute hypotensive state occurring with spinal anesthesia. It is also indicated as adjunctive treatment of hypotension due to hemorrhage, reactions to medications, surgical complications, and shock associated with brain damage due to trauma or tumor. Metaraminol acts on both α1-adrenergic receptors but appears to have no effect on β-adrenergic receptors. It acts by increasing the force of the heart's pumping action as well as constricting peripheral blood vessels.

C9H13NO2

167.207

167.095

54-49-9

33402-03-8 (tartrate);

5906

Typically exists as solid at room temperature

1.198g/cm3

357.9ºC at 760mmHg

107.5°C

170.3ºC

1.4760 (estimate)

1.473

3

3

2

12

141

2

C[C@@H]([C@@H](C1=CC=CC(O)=C1)O)N

WXFIGDLSSYIKKV-RCOVLWMOSA-N

InChI=1S/C9H13NO2/c1-6(10)9(12)7-3-2-4-8(11)5-7/h2-6,9,11-12H,10H2,1H3/t6-,9-/m0/s1

3-[(1R,2S)-2-amino-1-hydroxypropyl]phenol

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.)