GABAA receptor

Fospropofol, a phosphate ester ater soluble prodrug of propofol has been found to be safe and effective alternative to propofol and midazolam for use in endoscopic and other procedures. The unique pharmacology of fospropofol provides scope for expansion to introduce new drug options for sedation.Fospropofol gets converted to propofol by endothelial alkaline phosphatases5 Propofol is a agonist at GABAA receptor .It binds to a specific site on the a and 11 subunits of the receptor complex, but not to the GABA binding site. Activation of the GABAA receptor results in increased Cl-conductance and hyperpolarization, thus inhibiting the postsynaptic neuron. It also inhibits the excitatory NMDA glutamate receptors thus decreasing Ca++ entry resulting in postsynaptic inhibition. Above mechanisms results in sedation.[1]

A total of 347 (96.3%) and 175 (97.2%) patients in the intervention and control groups, respectively, completed the study. The success rate for the primary outcome was 97.7% for both study drugs. The most frequent AEs in the intervention group were abnormal feeling (62.0%), blood pressure reduction (13.5%), and injection site pain (13.3%). No AEs related to consciousness and mental and cognitive functions or serious adverse events were reported.[2]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of fospropofol during breastfeeding. However, fospropofol is rapidly metabolized to propofol in the body. Amounts of propofol in milk are very small and are not expected to be absorbed by the infant. Although one expert panel recommends withholding nursing for an unspecified time after propofol administration, most recommend that breastfeeding can be resumed as soon as the mother has recovered sufficiently from general anesthesia to nurse and that discarding milk is unnecessary. When a combination of anesthetic agents is used for a procedure, follow the recommendations for the most problematic medication used during the procedure. General anesthesia for cesarean section using propofol as a component for induction may delay the onset of lactation. In one study, breastfeeding before general anesthesia induction reduced requirements of propofol and sevoflurane compared to those of nursing mothers whose breastfeeding was withheld or nonnursing women. Case reports have noted green discoloration of breastmilk after nursing mothers received propofol.
◉ Effects in Breastfed Infants
Four mothers who were breastfeeding their infants received propofol as part of their general anesthesia for surgical procedures. All patients also received intravenous remifentanil and rocuronium, and inhaled xenon as part of the anesthesia. They were given doses of propofol that targeted a serum concentration of 6.5 mcg/L for induction and stopped as xenon anesthesia was started. Operation times ranged from 35 to 45 minutes. Individual infants were first breastfed as follows: 1.5 hours, 2.8 hours, 4.6 hours, and 5 hours after extubation. No signs of sedation were observed in any of the infants.
◉ Effects on Lactation and Breastmilk
Five women who were 6 to 15 weeks postpartum were given single doses of 2 mg of midazolam and 2.5 mg/kg of propofol intravenously before undergoing general anesthesia. The women's milk output following the surgical procedure was less than half of the normal milk output of nursing mothers. The authors speculated that milk volume might be reduced postoperatively because of perioperative fluid restriction and volume losses, as well as stress-induced inhibition of milk production.
A woman underwent emergency laparoscopic surgery using propofol as well as fentanyl, remifentanil, mivacurium, and dipyrone during the surgery and metamizole, piritramide, dipyrone, butylscopolamine, and metoclopramide postoperatively. Eight hours postoperatively, her milk turned bluish green, then green. Both propofol and metoclopramide have caused green urine. Thirty hours after the milk color change, propofol but not metoclopramide, was detected in milk.
A randomized study compared the effects of cesarean section using general anesthesia, spinal anesthesia, or epidural anesthesia, to normal vaginal delivery on serum prolactin and oxytocin as well as time to initiation of lactation. General anesthesia was performed using propofol 2 mg/kg and rocuronium 0.6 mg/kg for induction, followed by sevoflurane and rocuronium 0.15 mg/kg as needed. Fentanyl 1 to 1.5 mcg/kg was administered after delivery. Patients in the general anesthesia group (n = 21) had higher post-procedure prolactin levels and a longer mean time to lactation initiation (25 hours) than in the other groups (10.8 to 11.8 hours). Postpartum oxytocin levels in the nonmedicated vaginal delivery group were higher than in the general and spinal anesthesia groups.
A randomized, double-blind study compared the effects of intravenous propofol 0.25 mg/kg, ketamine 0.25 mg/kg, ketamine 25 mg plus propofol 25 mg, and saline placebo for pain control in mothers post-cesarean section in mothers post-cesarean section. A single dose was given immediately after clamping of the umbilical cord. The time to the first breastfeeding was 58 minutes in those who received placebo, 42.6 minutes with propofol and 25.8 minutes with propofol plus ketamine. The time was significantly shorter than the other groups with the combination.
A retrospective study of women in a Turkish hospital who underwent elective cesarean section deliveries compared women who received bupivacaine spinal anesthesia (n = 170) to women who received general anesthesia (n = 78) with propofol for induction, sevoflurane for maintenance and fentanyl after delivery. No differences in breastfeeding rates were seen between the groups at 1 hour and 24 hours postpartum. However, at 6 months postpartum, 67% of women in the general anesthesia group were still breastfeeding compared to 81% in the spinal anesthesia group, which was a statistically significant difference.]
A woman nursing an 8-month-old infant 6 to 8 times daily was admitted to the hospital for an appendectomy. During the procedure she received cefazolin, granisetron, ketorolac, rocuronium, succinylcholine, and sufentanil. The patient also received 2 boluses of intravenous propofol of 150 mg followed shortly thereafter by a 50 mg dose. Postoperatively, she was receiving acetaminophen, cefazolin, ibuprofen, and pantoprazole, as well as oxycodone and dimenhydrinate as needed. Twenty-two hours after the procedure, the mother extracted milk for the first time and noted it to be light green in color. Analysis of the green milk using a nonvalidated assay detected no propofol. The green color faded and was absent by postoperative day 4 when she resumed breastfeeding. The authors judged that the green color was possibly caused by propofol or one of its metabolites.
A pregnant woman had an emergency cesarean section delivery in her 24th week of gestation. During the procedure she received 200 mg of propofol as well as cefazolin and acetaminophen after delivery. The first milk expressed by the mother at 12 hours after the procedure was dark green. At 30 hours after the procedure is was light green and returned to a normal color by hour 48.

[1]. J Anaesthesiol Clin Pharmacol. 2011 Jan-Mar; 27(1): 79–83.
[2]. Front Pharmacol. 2021; 12: 687894.
[3]. A double-blind, randomized, multicenter, dose-ranging study to evaluate the safety and efficacy of fospropofol disodium as an intravenous sedative for colonoscopy in high-risk populations. Am J Ther. 2013 Mar-Apr;20(2):163-71.

See also: Propofol (has active moiety); Fospropofol (is salt form of).

C13H19NA2O5P

332.24

332.076

C, 47.00 H, 5.76 Na, 13.84 O, 24.08 P, 9.32

258516-87-9

258516-87-9(Disodium);258516-89-1(Free acid);258516-87-9

3038497

Typically exists as solid at room temperature

441.5ºC at 760mmHg

220.8ºC

1.43E-08mmHg at 25°C

4.255

0

5

5

21

285

0

[Na+].[Na+].O=P(OCOC1C(C(C)C)=CC=CC=1C(C)C)([O-])[O-]

LWYLQNWMSGFCOZ-UHFFFAOYSA-L

InChI=1S/C13H21O5P.2Na/c1-9(2)11-6-5-7-12(10(3)4)13(11)17-8-18-19(14,15)16;;/h5-7,9-10H,8H2,1-4H3,(H2,14,15,16);;/q;2*+1/p-2

[2,6-di(propan-2-yl)phenoxy]methyl phosphatedisodium

GPI-15715 GPI15715 lusedraFospropofol Disodium fospropofolGPI 15715 Aquavan Lusedra UNII-30868AY0IF

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.)