ABSTRACT
Benzimidazole 5-carboxylic acid derivatives were investigated for analgesic activity in this study. Of the benzimidazole compounds tested, 2-(2-nitro-phenyl)-1H-benzimidazole 5-carboxylic acid showed remarkable naloxone sensitive analgesic activity in the tail clamp but not in the tail immersion analgesia tests. This centrally active compound showed antispasmodic activity only on KCl induced contractions of isolated rat ileum and not on acetylcholine induced contractions. Acute toxicity of the compounds were >100 mg/kg i.p. mice. It was concluded that substitution of the 2(o-phenyl) by nitro- but not by chloro- or methoxy groups is important for naloxone sensititive analgesic activity of benzimidazole compounds and it was hypothetized that new imidazole compounds having a 2-(o-substituted phenyl) moiety needs to be investigated.
Subject(s)
Analgesics, Non-Narcotic/chemical synthesis , Analgesics, Non-Narcotic/pharmacology , Benzimidazoles/chemical synthesis , Benzimidazoles/pharmacology , Carboxylic Acids/chemical synthesis , Carboxylic Acids/pharmacology , Parasympatholytics/chemical synthesis , Parasympatholytics/pharmacology , Analgesics, Non-Narcotic/toxicity , Animals , Behavior, Animal/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Immersion/adverse effects , In Vitro Techniques , Lethal Dose 50 , Male , Mice , Pain Measurement/drug effects , Parasympatholytics/toxicity , Physical Stimulation , Structure-Activity RelationshipABSTRACT
4,4'-Dihydroxybenzophenone-2,4-ditrophenylhydrazone (A-007) has demonstrated anticancer activities, when administered topically to patients with metastatic cancer to the skin. Acute, subacute and subchronic dermal studies with A-007 in adult rabbits, rats, guinea pigs and monkeys failed to demonstrate local or systemic toxicity when applied topically as a 0.25% gel. A-007 did not penetrate the dermal lymphatics and did not produce detectable levels of A-007 in the plasma when applied as a 0.25% gel topically to skin. In the above studies, topically administered A-007 stimulated local sub-epithelial and dermal lymphocyte modulation, with increased CD8+ cytotoxic lymphocytes (CTL) noted, in guinea pig skin. Generally topical A-007 is well tolerated and may have useful immune modulation properties.
Subject(s)
Hydrazones/pharmacology , Phenols/pharmacology , Skin/drug effects , Absorption , Animals , Body Weight/drug effects , Chlorocebus aethiops , Female , Guinea Pigs , Hydrazones/administration & dosage , Hydrazones/chemistry , Hydrazones/toxicity , Male , Molecular Structure , Phenols/administration & dosage , Phenols/chemistry , Phenols/toxicity , Primates , Rabbits , Rats , Rodentia , Skin/immunologyABSTRACT
The essential oils of Nepeta species including Nepeta phyllochlamys P. H. Davis, N. nuda L. ssp. nuda, and N. caesarea Boiss. have been screened by use of the tail-flick and tail immersion (52.5 degrees C) methods. Of the species studied, only N. caesarea showed significant analgesic activity, besides marked sedation, which was also blocked by naloxone, indicating involvement of opioid receptors. Moreover, it was only active on mechanical, not thermal, algesic response which suggests specificity for specific opioid receptor subtypes, excluding mu-opioid receptors. Because 4a alpha,7alpha,7a alpha-nepetalactone is the main component of the essential oil of N. caesarea, and is present at very high levels (92-95%), it is concluded that 4a alpha,7alpha,7a alpha-nepetalactone is the active principle and has a specific opioid receptor subtype agonistic activity.
Subject(s)
Analgesia , Analgesics, Opioid/pharmacology , Cyclopentanes/pharmacology , Medicine, Traditional , Narcotic Antagonists , Plants, Medicinal , Pyrones/pharmacology , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/isolation & purification , Animals , Behavior, Animal/drug effects , Cyclopentane Monoterpenes , Cyclopentanes/administration & dosage , Cyclopentanes/isolation & purification , Female , Injections, Intraperitoneal , Male , Mice , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Pyrones/administration & dosage , Pyrones/isolation & purification , TurkeyABSTRACT
Hypericum species have been used as herbal remedies for the therapy of various diseases since ancient times. It has been reported that Hypericum perforatum is a useful herbal remedy for the treatment of neurological disorders such as coxalgia, menopausal neurosis, headache, hydrophobia, hypersensitivity, mental aliments, neuralgia, paralysis, spastic paralysis, spinal convulsion, spinal irritation, stiff neck, tetanus, etc. On the basis of recent clinical studies, the extracts prepared from H. perforatum have been found to be effective for the treatment of mild and moderate depressions with no special side effects. In the present study, the effects of H. perforatum and H. calycinum on the central nervous system were investigated using various behavioural models including swimming time, locomotor activity, tail-flick and hole-board experiments. According to the results obtained, it was found that the extracts prepared from Hypericum perforatum and Hypericum calycinum are as effective as antidepressant drugs, desipramine and trimipramine, which were used for the comparison of their effects with these two plant extracts in animal models. The findings obtained also suggested that the antidepressant effect of Hypericum calycinum may be as potent as that of Hypericum perforatum and may be used for therapeutic purposes in depression.
