NMDA Receptor

In the spinal dorsal horn, a region intimately associated with central sensitization, bucivacaine blocks NMDA receptor-mediated synaptic transmission [1]. Bupivacaine shifts the half-maximal activation/deactivation membrane potential toward a little more negative membrane potential, which changes the voltage dependency of channel activation and steady-state inactivation. SCN5A channels have a minor sensitivity to bupivacaine (IC50=2.18±0.16 μM) when they are in the inactive state [2]. With an IC50 of 16.5 μM, bupivacaine dose-dependently and reversibly blocks SK2 channels [3].

Absorption, Distribution and Excretion
Systemic absorption of local anesthetics depends on the administered dose and concentration, as well as the total amount administered. Other factors affecting the rate of systemic absorption include the route of administration, blood flow at the administration site, and the presence of adrenaline in the anesthetic solution. When bupivacaine reconstituted with meloxicam is administered via infusion, systemic parameters vary after a single dose. In patients undergoing hallux valgus resection, the Cmax of 60 mg bupivacaine was 54 ± 33 ng/mL, the median Tmax was 3 hours, and the AUC∞ was 1718 ± 1211 ngh/mL. In hernia repair using a 300 mg dose, the corresponding values were 271 ± 147 ng/mL, 18 hours, and 15,524 ± 8921 ngh/mL, respectively. Finally, when a 400 mg dose was used in total knee arthroplasty, the corresponding values were 695 ± 411 ng/mL, 21 hours, and 38,173 ± 29,400 ngh/mL, respectively. Only 6% of bupivacaine was excreted unchanged in the urine. After absorption into the bloodstream, bupivacaine hydrochloride exhibits a higher binding rate to plasma proteins than any other local anesthetic; the reported binding rate is 82-96%. Bupivacaine hydrochloride has the lowest placental translocation among all parenteral local anesthetics, and therefore may have the least inhibitory effect on the fetus. Pregnant rats were intravenously infused with bupivacaine at a rate of 0.33 mg·kg⁻¹·min⁻¹ over 15 minutes. The fetus was delivered at the end of the infusion or 2 or 4 hours after administration. Blood and tissue samples were collected from the mother and fetus, and bupivacaine and its metabolites were determined by capillary gas chromatography-mass spectrometry. The elimination half-life of bupivacaine is 37.7 minutes. The major metabolite is 3'-hydroxybupivacaine. At the end of administration, bupivacaine and 3'-hydroxybupivacaine were detected in all samples. The concentration ratio of bupivacaine in fetal plasma to maternal plasma was 0.29, and in the placenta it was 0.63. The highest concentration of bupivacaine was found in the amnion: three times that of maternal plasma and eleven times that of fetal plasma. Four hours after administration, bupivacaine was undetectable in all maternal and fetal samples, while 3'-hydroxybupivacaine remained in all tissues except fetal plasma and the heart. These data indicate that significant amounts of bupivacaine were absorbed by the bilateral placenta, amnion, and myometrium. 3'-hydroxybupivacaine was present in all tissues except fetal plasma and the heart, even though the maternal compound was undetectable. Following tail, epidural, or peripheral nerve block with bupivacaine hydrochloride, peak blood concentrations of bupivacaine are reached within 30 to 45 minutes, subsequently decreasing to negligible levels over the next 3 to 6 hours. Plasma pharmacokinetic studies following direct intravenous injection of bupivacaine hydrochloride have shown that it conforms to a three-compartment open model. The first compartment represents the rapid distribution of the drug within the blood vessels. The second compartment represents the equilibrium of the drug in highly perfused organs such as the brain, myocardium, lungs, kidneys, and liver. The third compartment represents the equilibrium of the drug in low-perfused tissues such as muscle and fat. Clearance from tissue distribution depends primarily on the ability of binding sites in the circulatory system to transport the drug to the liver for metabolism. For more complete data on the absorption, distribution, and excretion of bupivacaine (6 items), please visit the HSDB records page. Metabolites/Metabolites Amide local anesthetics (such as bupivacaine) are primarily metabolized in the liver by binding to glucuronic acid. The major metabolite of bupivacaine is 2,6-piperidinimide, primarily catalyzed by cytochrome P450 3A4. Pregnant rats received intravenous infusion of bupivacaine at a rate of 0.33 mg·kg⁻¹·min⁻¹ over 15 minutes. The fetus was delivered at the end of the infusion or 2 or 4 hours after administration. Blood and tissue samples were collected from both mother and fetus, and bupivacaine and its metabolites were determined by capillary gas chromatography-mass spectrometry. The elimination half-life of bupivacaine was 37.7 minutes. The major metabolite was 3'-hydroxybupivacaine. Bupivacaine and 3'-hydroxybupivacaine were detected in all samples at the end of administration. The fetal-to-maternal concentration ratio of bupivacaine in plasma was 0.29, and in the placenta it was 0.63. The highest concentration of bupivacaine was found in the amnion: 3 times higher than in maternal plasma and 11 times higher than in fetal plasma. Four hours after administration, bupivacaine was undetectable in all maternal and fetal samples, while 3'-hydroxybupivacaine remained in all tissues except fetal plasma and the heart. These data indicate that significant amounts of bupivacaine were absorbed bilaterally by the placenta, as well as in the amnion and myometrium. Even though the maternal compound was undetectable, 3'-hydroxybupivacaine remained in all tissues except fetal plasma and the heart. Bupivacaine hydrochloride is primarily metabolized to piperidinyl dimethylamine (PPX) via N-dealkylation, a process that may occur in the liver. Bupivacaine is primarily excreted in the urine as a small amount of PPX, the unchanged drug (5%), and other unidentified metabolites. Amide-type local anesthetics (such as bupivacaine) are primarily metabolized in the liver via glucuronide conjugation. The major metabolite of bupivacaine is 2,6-piperidinimide, primarily catalyzed by cytochrome P450 3A4. Elimination pathway: Only 6% of bupivacaine is excreted unchanged in the urine. Half-life: 2.7 hours in adults, 8.1 hours in newborns. The median half-life of bupivacaine in combination with meloxicam for postoperative analgesia is 15-17 hours, depending on the dose and administration site. Pregnant rats received intravenous infusion of bupivacaine at a rate of 0.33 mg·kg⁻¹·min⁻¹ over 15 minutes. The fetus was delivered at the end of the infusion or 2 or 4 hours after administration. Blood and tissue samples were collected from the mother and fetus, and bupivacaine and its metabolites were determined by capillary gas chromatography-mass spectrometry. The elimination half-life of bupivacaine is 37.7 minutes. The elimination half-life of bupivacaine hydrochloride in adults is 1.5-5.5 hours, and in newborns it is 8.1 hours.

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Because bupivacaine has very low concentrations in breast milk and is not absorbed orally, the dose ingested by the infant is very small, therefore it has not caused any adverse effects on breastfed infants.
There have been reports that the combined use of bupivacaine with other anesthetics and analgesics during labor may interfere with breastfeeding. However, this assessment is controversial and complex due to the varying drug combinations, dosages, and patient populations involved in studies, as well as the differences in techniques used and flawed designs in many studies. In contrast, epidural bupivacaine initiated after umbilical cord ligation appears to improve breastfeeding success rates due to improved pain control. Overall, with good breastfeeding support, epidural bupivacaine, whether in combination with fentanyl or its derivatives, has little or no adverse effect on breastfeeding success rates. Labor analgesia may delay the onset of lactation.
◉ Effects on Breastfed Infants
No significant adverse reactions were observed in 13 breastfed infants whose mothers received epidural bupivacaine analgesia.
30 patients undergoing cesarean section received bilateral transversus abdominis plane block using a combination of 52 mg 0.25% bupivacaine hydrochloride and 266 mg 1.3% liposomal bupivacaine. Two infants experienced transient tachypnea, but the causal relationship could not be determined. During the 14-day follow-up period, none of the infants required readmission.
◉ Effects on Lactation and Breast Milk
30 women undergoing cesarean section received either spinal anesthesia (unspecified) (n = 15) or spinal anesthesia combined with bupivacaine (n = 15) followed by epidural infusion after umbilical cord ligation. The bupivacaine administration regimen was: an initial bolus dose of 12.5 mg, followed by a continuous infusion at a rate of 17.5 mg/hour for 3 days. Patients treated with bupivacaine experienced better pain relief, as evidenced by lower pain scores and a lower dosage of diclofenac sodium for analgesia. Furthermore, the daily milk production in the bupivacaine treatment group was higher than in the untreated group, and this difference was statistically significant from day 3 to day 11 postpartum (end of the study). The authors concluded that improved pain relief increased the success rate of breastfeeding. Twenty women who underwent cesarean section received either epidural bupivacaine or bupivacaine combined with buprenorphine after umbilical cord ligation. The bupivacaine administration regimen was: an initial bolus dose of 12.5 mg, followed by a continuous infusion of 17.5 mg/hour for 3 days. The buprenorphine administration regimen was: an initial bolus dose of 200 mcg, followed by a continuous infusion of 8.4 mcg/hour for 3 days. Breastfeeding began as soon as patients were able to sit up. Both groups of patients showed increased breast milk intake and infant weight within 10 days postpartum; however, the increase was greater in patients using bupivacaine alone. A prospective cohort study compared women who did not receive analgesia during labor (n = 63) with women who received continuous epidural analgesia with fentanyl combined with 0.05% to 0.1% bupivacaine (n = 39) or ropivacaine (n = 13). The total dose of bupivacaine ranged from 31 to 62 mg, and the mean total infusion time from initiation to delivery was 219 minutes. The study found no differences between the two groups in breastfeeding effectiveness or infant neurobehavioral status 8 to 12 hours postpartum, or in the number of infants exclusively or partially breastfed at 4 weeks postpartum. A randomized prospective study measured breastfeeding behavior in full-term healthy infants of 100 multiparous women who received epidural or intravenous fentanyl during labor. The epidural group initially received 100 mg bupivacaine via epidural injection, followed by a continuous infusion of 25 mg/hour. The intravenous fentanyl group received 15–20 mg bupivacaine via spinal injection. Breastfeeding behavior differed slightly between the two groups, with infants in the intravenous fentanyl group showing slightly less breastfeeding performance than those in the epidural group. However, all mothers were able to breastfeed within 24 hours. No serious breastfeeding problems were reported by any mother; 10 mothers in the epidural group reported mild to moderate breastfeeding problems, compared to 7 mothers in the intravenous fentanyl group. Twenty mothers in the epidural anesthesia group and 14 mothers in the intravenous anesthesia group used supplemental bottle feeding; the difference between the two groups was not statistically significant. A randomized, non-blinded study of women undergoing cesarean section compared the effects of epidural anesthesia with general anesthesia (induced by intravenous thiopental sodium 4 mg/kg and succinylcholine 1.5 mg/kg, followed by nitrous oxide and isoflurane). Results showed that the time to first breastfeeding was significantly shorter in the epidural anesthesia group than in the general anesthesia group (107 minutes vs. 228 minutes). This difference may be due to the effects of anesthesia on the infant, as infants in the general anesthesia group had significantly lower Apgar scores, neurological scores, and adaptation scores than the control group. A randomized, multicenter trial compared the breastfeeding initiation rate and duration in women receiving high-dose epidural bupivacaine monotherapy or a combination of two low-dose bupivacaines with fentanyl. This trial also compared a matched control group that did not receive epidural anesthesia. Results showed no difference in breastfeeding initiation rate and duration between the epidural anesthesia group and the non-epidural anesthesia group that did not receive medication. A non-randomized study of low-risk mothers and infants found no overall difference in neonatal sucking volume regardless of whether the mother received different doses of bupivacaine combined with fentanyl epidural infusion, different doses of fentanyl epidural infusion alone, or no labor analgesia. Subgroup analyses by sex and sucking frequency showed that high doses of bupivacaine and fentanyl had an effect on female infants but no effect on male infants. However, imbalances in many factors between study groups made the results difficult to interpret. In a prospective cohort study, 87 multiparous women received epidural bupivacaine and fentanyl analgesia during labor and vaginal delivery. The loading dose was 0.125% bupivacaine and 50–100 mcg fentanyl. Maintenance epidural analgesia was achieved using 0.0625% bupivacaine and 0.2 mcg/mL fentanyl. The median fentanyl dose received by women was 151 mcg (range 30–570 mcg). Women completed breastfeeding questionnaires at 1 week and 6 weeks postpartum. Most women had prior breastfeeding experience, had family support at home, and had adequate maternity leave. All women initiated breastfeeding at 1 week postpartum, and 95.4% were still breastfeeding at 6 weeks postpartum. A national survey of women from late pregnancy to 12 months postpartum and their infants compared the time to lactroogenesis II in mothers who received and did not receive pain medication during labor. Medication categories included: spinal or epidural anesthesia alone, spinal or epidural anesthesia combined with other medications, and other analgesics alone. Women who received any category of medication were approximately twice as likely to experience a delayed lactroogenesis II (>72 hours) compared to women who did not receive labor analgesia. A randomized study compared the effects of cesarean section under general anesthesia, spinal anesthesia, or epidural anesthesia versus vaginal delivery on serum prolactin and oxytocin levels and the time to lactation initiation. Spinal anesthesia used 10–11 mg of hypertonic 5% bupivacaine solution, while epidural anesthesia used 10 mL (50 mg) of 0.5% bupivacaine solution. After delivery, all patients received an intravenous infusion of 30 IU of oxytocin in 1 L of normal saline; if blood pressure was normal, 0.2 mg of ergonovine was added. Patients in the general anesthesia group (n = 21) had higher postoperative prolactin levels and a longer average time to lactation initiation (25 hours) than other groups (10.8–11.8 hours). Postpartum oxytocin levels were higher in the non-pharmacological vaginal delivery group than in the general anesthesia and spinal anesthesia groups, and serum oxytocin levels were higher in the epidural anesthesia group than in the spinal anesthesia group. A retrospective study in a Spanish public hospital compared infants born to mothers who received epidural anesthesia containing fentanyl and bupivacaine or ropivacaine during delivery. Infants born to mothers who received epidural anesthesia had lower rates of early breastfeeding. A randomized, double-blind study compared three epidural maintenance solutions used for labor analgesia: bupivacaine 1 mg/mL, bupivacaine 0.8 mg/mL plus fentanyl 1 mcg/mL, or bupivacaine 0.625 mg/mL plus fentanyl 2 mcg/mL. At 6 weeks postpartum, breastfeeding rates reached 94% or higher in all groups, with no significant difference between groups. All mothers delivered at term and had a strong desire to breastfeed; almost all mothers delivered vaginally. A prospective cohort study of 1204 Israeli women aimed to investigate the effectiveness of epidural analgesia during labor. This study employed the following protocol: 15 mL of 0.1% bupivacaine and 100 mcg fentanyl were administered in 5 mL increments, followed by continuous epidural infusion of 10 mL of 0.1% bupivacaine and 2 mcg/mL fentanyl in 5 mL increments, using a patient-controlled epidural analgesia (PCA) mode, with each additional 5 mL infusion and a lockout time of 15 minutes. At 6 weeks postpartum, mothers receiving epidural analgesia had lower rates of breastfeeding and exclusive breastfeeding (74% and 52%, respectively) than those not receiving epidural analgesia (83% and 68%, respectively). However, this difference was primarily due to parity, with minimal impact on multiparous women. A retrospective study compared women undergoing elective cesarean sections at a Turkish hospital, finding no difference in breastfeeding rates at 1 hour and 24 hours postpartum between women receiving bupivacaine spinal anesthesia (n = 170) and those receiving general anesthesia (n = 78). General anesthesia was induced with propofol, maintained with sevoflurane, and administered with fentanyl for postpartum anesthesia. However, at 6 months postpartum, 67% of women in the general anesthesia group were still breastfeeding, compared to 81% in the spinal anesthesia group – a statistically significant difference. A study of 169 pregnant women randomly assigned them to three groups, each receiving one of three solutions for epidural anesthesia during labor. One solution was a mixture of 0.1% or 0.125% bupivacaine with 5 micrograms of sufentanil, and another was a mixture of 0.1% bupivacaine with 10 micrograms of sufentanil, each in 15 ml volumes. There was no difference in mean LATCH scores among the three groups of infants. A Swedish observational study compared breastfeeding behavior in infants born to mothers who received intravenous or intramuscular oxytocin (regardless of whether they received concurrent epidural analgesia with sufentanil (median dose 10 micrograms) or bupivacaine (median dose 17.5 mg)). Infants born to mothers receiving only oxytocin infusion had comparable breastfeeding rates to infants born to mothers receiving no intervention. Mothers receiving oxytocin combined with epidural analgesia experienced reduced breastfeeding behavior and greater weight loss on postpartum day 2. Mothers of well-breastfed infants showed greater fluctuations in serum oxytocin levels than mothers of poorly breastfed infants. A non-randomized, non-blinded study conducted in a Serbian hospital included women near term undergoing cesarean section, comparing the effects of general anesthesia (n = 284) with spinal or epidural anesthesia (n = 249). Spinal anesthesia used hyperosmolar bupivacaine 12 mg and fentanyl 0.01 mg; epidural anesthesia used isotonic bupivacaine 0.5% (0.5 mg per 10 cm of height) and fentanyl 0.05 mg. General anesthesia was induced with propofol 2.3 mg/kg and succinylcholine 1.5 mg/kg followed by endotracheal intubation and inhalation of an anesthetic gas mixture and oxygen. Reports indicate that the pre-delivery nitric oxide (likely nitrous oxide) content in the gas was 50%, increasing to 67% post-delivery. Sevoflurane was also used in some cases. After delivery and umbilical cord clamping, the mothers received intravenous fentanyl 3 mcg/kg and rocuronium bromide 0.5 mg/kg to promote placental delivery. Post-operatively, neostigmine and atropine were used to reverse neuromuscular blockade. All patients received diclofenac sodium 1 mg/kg every 8 hours for 24 hours post-delivery. 98% of patients under general anesthesia also received 100 mg tramadol, and 78.5% received 1 g acetaminophen. Patients under regional anesthesia did not receive tramadol or acetaminophen. Lactation occurred earlier in patients receiving regional anesthesia (56% and 29% at 18 and 24 hours post-operation, respectively), while 86% of women under general anesthesia did not begin lactation until 36 to 48 hours post-operation.

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Protein binding
Bupivacaine has a protein binding rate of approximately 95%.

[1]. Actions of Bupivacaine, a widely used local anesthetic, on NMDA receptor responses. J Neurosci. 2015 Jan 14;35(2):831-42.

[2]. A Comparative Analysis of Bupivacaine and Ropivacaine Effects on Human Cardiac SCN5A Channels. Anesth Analg. 2015 Jun;120(6):1226-34.

[3]. Inhibition of Voltage-Gated Na+ Channels by Bupivacaine Is Enhanced by the Adjuvants Buprenorphine, Ketamine, and Clonidine. Reg Anesth Pain Med.Jul/Aug 2017;42(4):462-468.

1-Butyl-N-(2,6-dimethylphenyl)piperidin-2-carboxamide is a piperidine carboxamide formed by the condensation of the carboxyl group of N-butylpiperidinic acid with the amino group of 2,6-dimethylaniline. It is a piperidine carboxamide, aromatic amide, and tertiary amine compound. It is the conjugate base of 1-butyl-2-[(2,6-dimethylphenyl)carbamoyl]piperidinium. Bupivacaine is a widely used local anesthetic. Bupivacaine is an amide-based local anesthetic. The physiological effects of bupivacaine are achieved through local anesthesia. Bupivacaine is a long-acting amide-based local anesthetic. Bupivacaine reversibly binds to specific sodium ion channels on neuronal membranes, leading to a voltage-dependent decrease in membrane permeability to sodium ions, thereby stabilizing membrane structure; inhibiting depolarization and nerve impulse conduction; and causing reversible sensory loss. Liposomed bupivacaine is a liposomally encapsulated bupivacaine formulation. Bupivacaine is a long-acting local anesthetic of the amide class. Upon administration, bupivacaine reversibly binds to specific sodium ion channels on the neuronal membrane, leading to a voltage-dependent decrease in membrane permeability to sodium ions and stabilizing membrane structure. This results in inhibition of depolarization and nerve impulse conduction, leading to reversible sensory loss. Compared to bupivacaine alone, liposomal delivery prolongs the duration of local anesthesia and delays peak plasma concentration due to the slow release of bupivacaine from the liposomes. Bupivacaine is only present in individuals who have used or taken the drug. It is a widely used local anesthetic. Bupivacaine blocks the generation and conduction of nerve impulses by increasing the nerve electrical excitation threshold, slowing nerve impulse propagation, and reducing the rate of action potential rise. Bupivacaine binds to the intracellular portion of sodium channels, blocking sodium ion inflow into nerve cells, thereby preventing depolarization. Typically, the progression of anesthesia is related to the diameter of the affected nerve fiber, the degree of myelination, and the conduction velocity. Clinically, the order of loss of neurological function is as follows: (1) pain sensation, (2) temperature sensation, (3) touch sensation, (4) proprioception, (5) skeletal muscle tone. The analgesic effect of bupivacaine is thought to be related to its binding to the prostaglandin E2 receptor EP1 subtype (PGE2EP1), thereby inhibiting prostaglandin production and thus reducing fever, inflammation, and hyperalgesia.
A widely used local anesthetic.
See also: bupivacaine; meloxicam (ingredients).

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Drug Indications
As an implant, bupivacaine is indicated for adults after open inguinal hernia repair surgery, by placing the drug at the surgical site to produce postoperative analgesia for up to 24 hours. Bupivacaine liposome suspension is indicated for patients aged 6 years and older for single infiltration to produce postoperative local analgesia. In adults, it can also be used for brachial plexus interstitial block to produce postoperative regional analgesia. Bupivacaine, when used in combination with meloxicam, is indicated for postoperative analgesia within 72 hours after foot and ankle surgery, minor to medium-sized open abdominal surgery, and total lower extremity joint replacement surgery in adult patients. Bupivacaine, alone or in combination with epinephrine, is indicated for local or regional anesthesia or analgesia in adult patients for surgical, dental and oral surgery, diagnostic and therapeutic procedures, and obstetric procedures. Specific concentrations and formulations are recommended for each type of nerve block used to produce local or regional anesthesia or analgesia. Finally, due to the significant clinical risks associated with its use, bupivacaine is not recommended for all nerve blocks.
FDA Label
Exparel® Liposomes are indicated for: adult patients for brachial plexus or femoral nerve blocks to treat postoperative pain. Also indicated for adults 6 years and older and children as a local anesthetic for postoperative somatic pain from minor to medium-sized surgical wounds.
Postoperative Analgesia
Mechanism of Action
Similar to lidocaine, bupivacaine is an amide-type local anesthetic that exerts its local anesthetic effect by blocking the generation and conduction of nerve impulses. These impulses, also known as action potentials, are primarily dependent on membrane depolarization caused by the influx of sodium ions into neurons through voltage-gated sodium channels. Bupivacaine crosses the neuronal membrane and exerts its anesthetic effect by blocking the intracellular portion of the transmembrane pores of these channels. This blocking effect is use-dependent; repeated or prolonged depolarization enhances the blocking effect of sodium channels. Because sodium ions cannot pass through the channel pores, bupivacaine stabilizes the cell membrane at rest, thereby preventing the transmission of neurotransmitters. Generally, the progression of anesthesia is related to the diameter of the affected nerve fiber, the degree of myelination, and the conduction velocity. Clinically, the order of loss of neurological function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, (5) skeletal muscle tone. Although the primary mechanism of action of bupivacaine, which is the blocking of sodium channels, is well established, its other analgesic effects may be related to its binding to the prostaglandin E2 receptor EP1 subtype (PGE2EP1), which inhibits prostaglandin production, thereby reducing fever, inflammation, and hyperalgesia. Local anesthetics work by blocking the generation and conduction of nerve impulses. The mechanism may be to increase the electrical excitation threshold of the nerve, slow down the propagation speed of nerve impulses, and reduce the rate of rise of action potentials. Generally, the progression of anesthesia is related to the diameter of the affected nerve fibers, the degree of myelination, and the conduction velocity. Clinically, the order of loss of nerve function is as follows: (1) pain sensation, (2) temperature sensation, (3) touch sensation, (4) proprioception, and (5) skeletal muscle tone.

C18H31CLN2O2

342.9039

342.207

73360-54-0

Bupivacaine;38396-39-3;Bupivacaine hydrochloride;18010-40-7;Bupivacaine-d9;474668-57-0

2474

Typically exists as solid at room temperature

255-259℃

5.221

1

2

5

21

321

0

Cl[H].O=C(C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])N([H])C1C(C([H])([H])[H])=C([H])C([H])=C([H])C=1C([H])([H])[H].O([H])[H]

LEBVLXFERQHONN-UHFFFAOYSA-N

InChI=1S/C18H28N2O/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21)

1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide

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.

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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).

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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)

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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).

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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

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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.

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