Anticonvulsant Activities of 4–Bromobenzaldehyde Semicarbazone

Abstract

Some of the properties of 4-bromobenzaldehyde semicarbazone (compound IV), a prototype molecule of a new class of anticonvulsants, aryl semicarbazones, are described. Compound IV demonstrated activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests in mice, with low neurotoxicity. When given orally to rats, it displayed high potency in the MES test and very low neurotoxicity, resulting in a high protective index (PI). Compound IV displayed no proconvulsant properties, and development of rapid tolerance was not noted. When administered intraperitoneally (i.p.) at doses of 100, 300, or 600 mg/kg to peritoneally (i.p.) at doses of 100, 300, or 600 mg/kg to rats, compound IV had no effect on levels of gamma-aminobutyric acid (GABA) or on GABA-T activity in whole brain. When tested in vitro, compound IV had no effect on rat brain GABA-T at a drug concentration of 100 microM. Although the activities of certain drug-metabolizing enzymes were increased after oral administration of compound IV to rats, these effects were less prominent than those of phenytoin (PHT) and carbamazepine (CBZ). The principal mode of action of compound IV does not appear to be an interaction with the GABAA receptor complex, and other mechanisms, involving excitatory amino acid neurotransmission, will have to be considered in future investigations of the anticonvulsant activity of this compound.

Anticonvulsant and Sedative-Hypnotic Activities of N-Substituted Isatin Semicarbazones

“…pBromophenyl substituted derivative (3) was considered to be more active in MES (100 mg/kg) screen. This is in accordance with the observation for p-bromophenyl substituted semicarbazone [8]. All the compounds were less active than Dimmock's compound (4-(4-fluorophenoxy)-benzaldehyde semicarbazone) [21].…”

Anticonvulsant and Sedative-Hypnotic Activities of N-Substituted Isatin Semicarbazones

“…pBromophenyl substituted derivative (3) was considered to be more active in MES (100 mg/kg) screen. This is in accordance with the observation for p-bromophenyl substituted semicarbazone [8]. All the compounds were less active than Dimmock's compound (4-(4-fluorophenoxy)-benzaldehyde semicarbazone) [21].…”

Anticonvulsant activities of 4-(4?-fluorophenoxy) benzaldehyde semicarbazone

“…Previous studies revealed that 7-day treatment with 100 mg/kg of phenytoin daily led to percentage increases of cytochrome P-450, 4-nitroanisole O-demethylase, and UDP-glucuronosyltransferase of 52, 220, and 12, respectively. The comparable figures for carbamazepine were 45, 210, and 27 [Dimmock and Baker, 1994]. All of these figures were statistically different from control values except for the UDP-glucuronosyltransferase data for phenytoin.…”

Synthesis and In Vivo Anticonvulsant Activity of 2‐Methyl‐2‐[3‐(5‐piperazin‐1‐yl‐[1,3,4]oxadiazol‐2‐yl)‐phenyl]‐propionitrile Derivatives

“…In this connection, different electron‐donating or electron‐withdrawing groups attached to phenyl ring as substituent linked to sulfonyl group are studied for anticonvulsant efficacy. In the present series of compounds, the active compounds possess the entire requirements essential for anticonvulsant activity as proposed by Dimmock et al . On correlating the structures of the synthesized compounds with their anticonvulsant activity, it has been observed that compounds bearing the groups halogens on phenyl ring possess high potency in MES.…”

Anticonvulsant and Sedative-Hypnotic Activities of N-Substituted Isatin Semicarbazones

“…pBromophenyl substituted derivative (3) was considered to be more active in MES (100 mg/kg) screen. This is in accordance with the observation for p-bromophenyl substituted semicarbazone [8]. All the compounds were less active than Dimmock's compound (4-(4-fluorophenoxy)-benzaldehyde semicarbazone) [21].…”

Anticonvulsant activities of 4-(4?-fluorophenoxy) benzaldehyde semicarbazone

“…Previous studies revealed that 7-day treatment with 100 mg/kg of phenytoin daily led to percentage increases of cytochrome P-450, 4-nitroanisole O-demethylase, and UDP-glucuronosyltransferase of 52, 220, and 12, respectively. The comparable figures for carbamazepine were 45, 210, and 27 [Dimmock and Baker, 1994]. All of these figures were statistically different from control values except for the UDP-glucuronosyltransferase data for phenytoin.…”

Synthesis and In Vivo Anticonvulsant Activity of 2‐Methyl‐2‐[3‐(5‐piperazin‐1‐yl‐[1,3,4]oxadiazol‐2‐yl)‐phenyl]‐propionitrile Derivatives

“…In this connection, different electron‐donating or electron‐withdrawing groups attached to phenyl ring as substituent linked to sulfonyl group are studied for anticonvulsant efficacy. In the present series of compounds, the active compounds possess the entire requirements essential for anticonvulsant activity as proposed by Dimmock et al . On correlating the structures of the synthesized compounds with their anticonvulsant activity, it has been observed that compounds bearing the groups halogens on phenyl ring possess high potency in MES.…”

Anticonvulsant and Sedative-Hypnotic Activities of N-Substituted Isatin Semicarbazones

“…pBromophenyl substituted derivative (3) was considered to be more active in MES (100 mg/kg) screen. This is in accordance with the observation for p-bromophenyl substituted semicarbazone [8]. All the compounds were less active than Dimmock's compound (4-(4-fluorophenoxy)-benzaldehyde semicarbazone) [21].…”

Anticonvulsant activities of 4-(4?-fluorophenoxy) benzaldehyde semicarbazone

“…Previous studies revealed that 7-day treatment with 100 mg/kg of phenytoin daily led to percentage increases of cytochrome P-450, 4-nitroanisole O-demethylase, and UDP-glucuronosyltransferase of 52, 220, and 12, respectively. The comparable figures for carbamazepine were 45, 210, and 27 [Dimmock and Baker, 1994]. All of these figures were statistically different from control values except for the UDP-glucuronosyltransferase data for phenytoin.…”

Synthesis and In Vivo Anticonvulsant Activity of 2‐Methyl‐2‐[3‐(5‐piperazin‐1‐yl‐[1,3,4]oxadiazol‐2‐yl)‐phenyl]‐propionitrile Derivatives

“…In this connection, different electron‐donating or electron‐withdrawing groups attached to phenyl ring as substituent linked to sulfonyl group are studied for anticonvulsant efficacy. In the present series of compounds, the active compounds possess the entire requirements essential for anticonvulsant activity as proposed by Dimmock et al . On correlating the structures of the synthesized compounds with their anticonvulsant activity, it has been observed that compounds bearing the groups halogens on phenyl ring possess high potency in MES.…”