Inhibition of R-[3H]-baclofen binding to rat brain synaptic membranes by a homologous series of phenyl alcohol amides anticonvulsants and their evaluation as GABAB receptor blockers. 1998

S E Meza-Toledo, and D Martínez-Muñoz, and G Carvajal-Sandoval
Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, México D.F., México.

The inhibition of the specific R-[3H]-baclofen binding to GABAB (gamma-aminobutyric acid) sites by a homologous series of phenyl alcohol amides was tested in rat brain synaptic membranes. Some of these phenyl alcohol amides were designed as anticonvulsants as well as antagonists of the GABAB receptor. These anticonvulsants showed a high affinity to the GABAB receptor. DL-2-hydroxy-2-(4'-chlorophenyl)butyramide and DL-3-hydroxy-3-(4'-chlorophenyl)pentanamide (DL-Cl-HEPP) were as effective as GABA and R-baclofen and were the most potent examined. DL-2-hydroxy-2-phenylbutyramide (DL-HEPA), (+)-HEPA, (-)-HEPA, DL-3-hydroxy-3-phenylpentanamide (DL-HEPP) and DL-4-hydroxy-4-phenylhexanamide (DL-HEPB) were as potent as DL-baclofen. The phenyl alcohol amides with fluorine in the para position of the phenyl ring were less active than DL-2-hydroxysaclofen. DL-4-hydroxy-4-(4'-chlorophenyl)hexanamide was the least active of the series. In addition, R-baclofen antagonized very effectively the anticonvulsant activity of both DL-HEPP and DL-Cl-HEPP in a dose-dependent fashion. These results support the assumption that some of these phenyl alcohol amides anticonvulsants are GABAB receptor blockers.

UI MeSH Term Description Entries
D008297 Male Males
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D000577 Amides Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed) Amide
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D001418 Baclofen A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. Baclophen,Chlorophenyl GABA,Apo-Baclofen,Atrofen,Ba-34,647,Ba-34647,Baclofen AWD,Baclofène-Irex,Baclospas,CIBA-34,647-BA,Clofen,Gen-Baclofen,Genpharm,Lebic,Lioresal,Liorésal,Nu-Baclo,PCP-GABA,PMS-Baclofen,beta-(Aminomethyl)-4-chlorobenzenepropanoic Acid,beta-(p-Chlorophenyl)-gamma-aminobutyric Acid,AWD, Baclofen,Apo Baclofen,ApoBaclofen,Ba34,647,Ba34647,Baclofène Irex,BaclofèneIrex,CIBA34,647BA,GABA, Chlorophenyl,Gen Baclofen,GenBaclofen,Nu Baclo,NuBaclo,PMS Baclofen,PMSBaclofen
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013570 Synaptic Membranes Cell membranes associated with synapses. Both presynaptic and postsynaptic membranes are included along with their integral or tightly associated specializations for the release or reception of transmitters. Membrane, Synaptic,Membranes, Synaptic,Synaptic Membrane
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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