N-Benzoyl-GABA

N-Benzoyl-GABA
Clinical data
Other names	N-Benzoyl-γ-aminobutyric acid; N-Benzoyl-gamma-aminobutyric acid
ATC code	None;
Identifiers
	IUPAC name 4-benzamidobutanoic acid;
CAS Number	35340-63-7;
PubChem CID	37118;
ChEMBL	ChEMBL122303;
CompTox Dashboard (EPA)	DTXSID00188837 ;
Chemical and physical data
Formula	C11H13NO3
Molar mass	207.229 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CC=C(C=C1)C(=O)NCCCC(=O)O;
	InChI InChI=1S/C11H13NO3/c13-10(14)7-4-8-12-11(15)9-5-2-1-3-6-9/h1-3,5-6H,4,7-8H2,(H,12,15)(H,13,14); Key:BOZHPKGNNJPZKV-UHFFFAOYSA-N;

N-Benzoyl-GABA is a claimed GABA receptor agonist and derivative of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).^[1]^[2]^[3]^[4] It is said to be a lipophilic prodrug of GABA that in contrast to GABA itself is able to cross the blood–brain barrier.^[1]^[2]^[5]^[4] The drug produces anticonvulsant effects in rodents.^[4] It was first described in the scientific literature by 1978.^[4]

References

1 2 Greig NH (1989). "Drug Delivery to the Brain by Blood-Brain Barrier Circumvention and Drug Modification". Implications of the Blood-Brain Barrier and Its Manipulation. Boston, MA: Springer US. pp. 311–367. doi:10.1007/978-1-4613-0701-3_12. ISBN 978-1-4612-8039-2. The development of carboxyl-linked prodrugs for brain delivery has met with mixed success. Considerable effort has been channeled into the evolution of GABA-mimetics that are capable of entering the brain. The central inhibitory neurotransmitter GABA (Fig. 19) is a zwitterion at physiologic pH, pKa 4.0 and 10.7, and minimally penetrates the BBB. A variety of potential GABA prodrugs have been synthesized to mask the amino group by acylation 79; these have included N-pivaloyl and N-benzoyl-GABA. 82 Both compounds appeared to enter the brains of rats in significant amounts, reaching peak concentrations at 30 and 5 min, respectively. However, the in vivo enzymatic cleavage of such amides has proved difficult in humans.
1 2 Meldrum B (1984). "Amino acid neurotransmitters and new approaches to anticonvulsant drug action". Epilepsia. 25 Suppl 2: S140–S149. doi:10.1111/j.1528-1157.1984.tb05646.x. PMID 6146519.
↑ Kopelevich VM, Bulanova LN, Grigor'ev IA, Gorbunov SG, Sabanov AV, Adzhienko VL, et al. (1997). "Synthesis and study of psychotropic and hypotensive properties of new picamilon derivatives". Pharmaceutical Chemistry Journal. 31 (10): 536–539. doi:10.1007/BF02464261. ISSN 0091-150X.
1 2 3 4 Galzigna L, Garbin L, Bianchi M, Marzotto A (September 1978). "Properties of two derivatives of gamma-aminobutyric acid (GABA) capable of abolishing Cardiazol- and bicuculline-induced convulsions in the rat". Archives Internationales de Pharmacodynamie et de Therapie. 235 (1): 73–85. PMID 736693.
↑ Malakoutikhah M, Prades R, Teixidó M, Giralt E (March 2010). "N-methyl phenylalanine-rich peptides as highly versatile blood-brain barrier shuttles". Journal of Medicinal Chemistry. 53 (6): 2354–2363. doi:10.1021/jm901654x. PMID 20170117. Galzigna et al.41 demonstrated that N-benzoyl-GABA and N-pivaloyl-GABA, in contrast to GABA, crossed the BBB in rats and were cleaved enzymatically to release GABA.

[Greig1989-1] 1 2 Greig NH (1989). "Drug Delivery to the Brain by Blood-Brain Barrier Circumvention and Drug Modification". Implications of the Blood-Brain Barrier and Its Manipulation. Boston, MA: Springer US. pp. 311–367. doi:10.1007/978-1-4613-0701-3_12. ISBN 978-1-4612-8039-2. The development of carboxyl-linked prodrugs for brain delivery has met with mixed success. Considerable effort has been channeled into the evolution of GABA-mimetics that are capable of entering the brain. The central inhibitory neurotransmitter GABA (Fig. 19) is a zwitterion at physiologic pH, pKa 4.0 and 10.7, and minimally penetrates the BBB. A variety of potential GABA prodrugs have been synthesized to mask the amino group by acylation 79; these have included N-pivaloyl and N-benzoyl-GABA. 82 Both compounds appeared to enter the brains of rats in significant amounts, reaching peak concentrations at 30 and 5 min, respectively. However, the in vivo enzymatic cleavage of such amides has proved difficult in humans.

[Meldrum1984-2] 1 2 Meldrum B (1984). "Amino acid neurotransmitters and new approaches to anticonvulsant drug action". Epilepsia. 25 Suppl 2: S140–S149. doi:10.1111/j.1528-1157.1984.tb05646.x. PMID 6146519.

[KopelevichBulanovaGrigor'ev1997-3] Kopelevich VM, Bulanova LN, Grigor'ev IA, Gorbunov SG, Sabanov AV, Adzhienko VL, et al. (1997). "Synthesis and study of psychotropic and hypotensive properties of new picamilon derivatives". Pharmaceutical Chemistry Journal. 31 (10): 536–539. doi:10.1007/BF02464261. ISSN 0091-150X.

[GalzignaGarbinBianchi1978-4] 1 2 3 4 Galzigna L, Garbin L, Bianchi M, Marzotto A (September 1978). "Properties of two derivatives of gamma-aminobutyric acid (GABA) capable of abolishing Cardiazol- and bicuculline-induced convulsions in the rat". Archives Internationales de Pharmacodynamie et de Therapie. 235 (1): 73–85. PMID 736693.

[MalakoutikhahPradesTeixidó2010-5] Malakoutikhah M, Prades R, Teixidó M, Giralt E (March 2010). "N-methyl phenylalanine-rich peptides as highly versatile blood-brain barrier shuttles". Journal of Medicinal Chemistry. 53 (6): 2354–2363. doi:10.1021/jm901654x. PMID 20170117. Galzigna et al.41 demonstrated that N-benzoyl-GABA and N-pivaloyl-GABA, in contrast to GABA, crossed the BBB in rats and were cleaved enzymatically to release GABA.

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[2]

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[4]

[5]

See also

References