No abstract available.
*Aging ; Alzheimer Disease/drug therapy/economics/*pathology ; Cost of Illness ; Excitatory Amino Acid Agonists/therapeutic use ; Health Behavior ; Humans ; N-Methylaspartate/therapeutic use ; Risk Factors

Alzheimer's disease (AD) is the most common form of dementia caused by neurodegenerative process and is tightly related to amyloid beta (Abeta) and neurofibrillary tangles. The lack of early diagnostic biomarker and therapeutic remedy hinders the prevention of increasing population of AD patients every year. In spite of accumulated scientific information, numerous clinical trials for candidate drug targets have failed to be preceded into therapeutic development, therefore, AD-related sufferers including patients and caregivers, are desperate to seek the solution. Also, effective AD intervention is desperately needed to reduce AD-related societal threats to public health. In this review, we summarize various drug targets and strategies in recent preclinical studies and clinical trials for AD therapy: Allopathic treatment, immunotherapy, Abeta production/aggregation modulator, tau-targeting therapy and metabolic targeting. Some has already failed in their clinical trials and the others are still in various stages of investigations, both of which give us valuable information for future research in AD therapeutic development.
Alzheimer Disease/immunology/pathology/*therapy ; Amyloid beta-Peptides/antagonists & inhibitors/immunology/metabolism ; Antibodies, Monoclonal/therapeutic use ; Brain/metabolism/pathology ; Humans ; Immunotherapy ; N-Methylaspartate/therapeutic use ; tau Proteins/antagonists & inhibitors/metabolism

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence.These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence.
gamma-Aminobutyric Acid/metabolism ; Taurine/analogs & derivatives/therapeutic use ; Recurrence ; Receptors, Opioid, mu/genetics/metabolism ; Receptors, Opioid/antagonists & inhibitors ; Polymorphism, Genetic ; Neurons/metabolism ; Naltrexone/therapeutic use ; N-Methylaspartate/metabolism ; Models, Neurological ; Models, Biological ; Humans ; Glutamine/metabolism ; Disulfiram/therapeutic use ; Alcoholism/*drug therapy ; Alcohol Deterrents/*therapeutic use

OBJECTIVETo study different effects of Herba Lycopodii (HL) Alcohol Extracted Granule combined methylprednisolone on behavioral changes, brain derived neurotrophic factor (BDNF) expression levels, and N-methyl-D-aspartate (NMDA) receptor levels in rats with spinal cord injury (SCI).

METHODSMale adult SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the HL treatment group, the methylprednisolone treatment group, the HL + methylprednisolone treatment group. Rats in the HL treatment group were intragastrically administered with HL at the daily dose of 50 mg/kg for 5 successive days. Rats in the methylprednisolone treatment group were intramuscularly injected with 50 mg/kg methylprednisolone within 8 h after spinal cord contusion, and then the dose of methylprednisolone was reduced for 10 mg/kg for 5 successive days. Rats in the HL + methylprednisolone treatment group received the two methods used for the aforesaid two groups. Basso Beattie and Bresnahan (BBB) score (for hindlimb motor functions) were assessed at day 0, 3, 7, and 28 after operation. At day 13 after SCI, injured spinal T8-10 was taken from 8 rats of each group and stored in liquid nitrogen. The N-methyl-D-aspartate (NMDA) receptor affinity (Kd) and the maximal binding capacity (Bmax) were determined using [3H]MK-801 radioactive ligand assay. Rats' injured spinal cords were taken for immunohistochemical assay at day 28 after SCI. Expression levels of BDNF in the ventral and dorsal horn of the spinal cord were observed.

RESULTSCompared with the sham-operation group, the number of BDNF positive neurons in the ventral and dorsal horn of the spinal cord increased in the model group, Bmax increased (470 ± 34), Kd decreased, and BBB scores decreased at day 3 -28 (all P <0. 05). Compared with the SCI model group, the number of BDNF positive neurons and Kd increased, BBB scores at day 3 -28 increased (P <0. 05) in each medicated group. Bmax was (660 ± 15) in the methylprednisolone treatment group, (646 ± 25) in the HL treatment group, and (510 ± 21) in the HL +methylprednisolone treatment group (P <0. 05). Compared with the methylprednisolone treatment group, the number of BDNF positive neurons and Kd increased, BBB scores at day 7 -28 increased, and Bmax decreased in the HL treatment group and the HL + methylprednisolone treatment group (all P <0. 05). Compard with the HL treatment group, the number of BDNF positive neurons and Kd increased, and Bmax decreased (all P < 0.05).

CONCLUSIONSHL could effectively improve motor functions of handlimbs, increase expression levels of BDNF in the spinal cord, and lessen secondary injury by affecting spinal levels of NMDA receptors. It showed certain therapeutic and protective roles in treating SCI. Its effect was better than that of methylprednisolone with synergism.

Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ethanol ; Male ; Methylprednisolone ; pharmacology ; therapeutic use ; Models, Animal ; N-Methylaspartate ; metabolism ; Neurons ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; Spinal Cord Injuries ; drug therapy ; metabolism

AIMTo test the antiepileptic effect of phencynonate hydrochloride and investigate its antiepileptic mechanism.

METHODSThrough establishment of different epilepsy models, antiepileptic effects of phencynonate hydrochloride and other drugs were examined. Besides, the effect of phencynonate hydrochloride and other compounds against NMDA-induced lethality in mice, NMDA-induced injury in rat primary hippocampal neuronal cultures and NMDA-induced current were also observed.

RESULTSPhencynonate hydrochloride produced a significant anticonvulsant effect on different epilepsy models. Furthermore, phencynonate hydrochloride also exerted its obvious protection against the lethal effects of NMDA in mice, antagonized the NMDA-induced injury in rat primary hippocampal neuronal cultures and blocked NMDA-induced current in a dose-dependent manner.

CONCLUSIONPhencynonate hydrochloride had a notable anticonvulsant effect on typical epilepsy models, its antiepileptic mechanism might relate to its antagonism against NMDA receptor.

Animals ; Animals, Newborn ; Anticonvulsants ; pharmacology ; therapeutic use ; Aza Compounds ; pharmacology ; therapeutic use ; Cells, Cultured ; Electroshock ; Female ; Glycolates ; pharmacology ; therapeutic use ; Hippocampus ; cytology ; Lethal Dose 50 ; Male ; Mice ; N-Methylaspartate ; toxicity ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Pentylenetetrazole ; Rats ; Rats, Wistar ; Seizures ; chemically induced ; drug therapy