strychnine and Sleep-Initiation-and-Maintenance-Disorders

This study investigated the hypnotic, anti-convulsant and anxiolytic effects of 1-nitro-2-phenylethane (BPNE) obtained from the oil of Dennettia tripetala G. Baker (Annonaceae) and established its mechanism of action. The essential oil (EO) from the leaf, fruit and seed was obtained by hydrodistillation, followed by isolation of BPNE purified to 99.2% by accelerated gradient chromatography on silica, and identified by NMR and GC-MS. The pure BPNE and EO of the dried seed (93.6%) were comparatively evaluated for hypnotic, anticonvulsant and anxiolytic effects in mice. The acute toxicity of BPNE was determined and the LD50 was 490 mg/kg, intrapritonealy. The hypnotic activities of the EO and BPNE (50-400 mg/kg, i.p.) were assessed by loss of righting reflex, while sodium pentobarbitone (PBS) and diazepam (DZM) were used as positive controls. The anticonvulsant and anxiolytic effects of the EO and BPNE were evaluated in mice. Both BPNE and EO at doses ≥100 mg/kg induced spontaneous hypnosis with loss of righting reflex, significantly decreased sleep latency (SL) and also increased total sleeping time (TST) dose-dependently. They had comparable activity with NAP in TST. The BPNE exhibited higher hypnotic potency than EO at the same dose levels. The EO and BPNE offered comparable dose-related protections against PTZ- and strychnine-induced convulsions. Flumazenil (2 mg/kg) blocked the hypnotic and anticonvulsant (PTZ-convulsions) effects of both EO and BPNE. The essential oil at 5-20 mg/kg dose levels significantly (p<0.05) increased the percentage time spent and number of entries into the open arms. While at the same dose range BPNE significantly (p<0.05) increased the percentage time spent and the number of entries into the open arms respectively. The study concluded that 1-nitro-2-phenylethane exhibited dose dependent significant hypnotic, anticonvulsant and anxiolytic effects and it is the compound largely responsible for the neuropharmacological effects of the oil.

Topics: Animals; Annonaceae; Anti-Anxiety Agents; Anticonvulsants; Anxiety; Avoidance Learning; Benzene Derivatives; Dose-Response Relationship, Drug; Female; Flumazenil; GABA Modulators; Hypnotics and Sedatives; Male; Mice; Oils, Volatile; Phytotherapy; Plant Extracts; Plant Structures; Reflex, Righting; Seizures; Sleep; Sleep Initiation and Maintenance Disorders; Strychnine

Acanthus montanus, Alchornea laxiflora, Hyptis spicigera, Microglossa pyrifolia, Piliostigma reticulatum, and Voacanga africana were evaluated with respect to anticonvulsant and sedative activity in mice using animal models (maximal electroshock (MES), N-methyl-D-aspartate (NMDA), pentylenetetrazol (PTZ), isonicotinic hydrazide acid (INH), picrotoxin (PIC), and strychnine (STR)-induced convulsions or turning behavior and diazepam-induced sleep). Acanthus montanus protected 66.6% of mice against MES-, PIC-, and STR-induced convulsions and 83.3% of mice from PTZ-induced convulsions. Alchornea laxiflora protected 75% and 87.5% of mice in the STR and NMDA tests, respectively, at a dose of 120 mg/kg. Hyptis spicigera protected 100 and 87.5% of mice against STR- and PTZ-induced convulsions, respectively, at a dose of 160 mg/kg. Microglossa pyrifolia protected 50% to 100% of mice against convulsions. Piliostigma reticulatum protected 62.5% to 100% of mice against convulsions and turning behavior. Voacanga africana protected 62.5% to 87.5% of mice against convulsions and turning behavior. All of the plants except A. laxiflora also exerted sedative activity by strongly increasing the total duration of sleep induced by diazepam.

Topics: Animals; Anticonvulsants; Convulsants; Diazepam; Dose-Response Relationship, Drug; Electroshock; Epilepsy; Excitatory Amino Acid Agonists; Hypnotics and Sedatives; Isoniazid; Male; Medicine, African Traditional; Mice; N-Methylaspartate; Pentylenetetrazole; Picrotoxin; Plants, Medicinal; Sleep Initiation and Maintenance Disorders; Stereotyped Behavior; Strychnine