The pharmacological importance of agmatine in the brain

Agmatine is a polyamine that is produced via decarboxylation of l-arginine by the enzyme arginine decarboxylase. It binds to various receptors and has been accepted as a novel neurotransmitter in brain. In experimental studies, agmatine exhibited anticonvulsant, antinociceptive, anxiolytic and antidepressantlike actions. Furthermore, it has some beneficial effects on cerebral ischemia models in animals. Agmatine interacts with the mechanisms of withdrawal syndromes for several addictive agents. It also modulates some processes involved in learning and memory. Thus, agmatine seems to be a valuable agent for the treatment of behavioral and neurodegenerative disorders. However, the aberrant release and transmission of agmatine in the central nervous system (CNS) may be associated with mechanisms of several CNS disorders, such as psychosis. Interactions between agmatine and other central neurotransmitter systems, such as the glutamatergic and nitrergic systems, are also very important. In light of the current literature on agmatine, we can anticipate that the central agmatinergic system may be an important target in development of novel strategies and approaches for understanding the etiopathogenesis of some important central disorders and their pharmacological treatments. The main objective of this review is to investigate and update the information on effects of agmatine in CNS and highlight its pharmacological importance in central disorders

A new target for diagnosis and treatment of CNS disorders: Agmatinergic system.

A polyamine agmatine is produced through decarboxylation of L -arginine by the enzyme arginine decarboxylase and is a new neurotransmitter in central nervous system (CNS). It has been suggested that agmatine has analgesic, anxiolytic and antidepressant activities in animals. In experimental studies, it also generates some favorable effects on cerebral damages and withdrawal syndromes involved in addictive drugs. Furthermore, it modulates some processes of learning and memory. Thus, agmatine may be an important target for the treatment of CNS disorders. However, the abnormal release and transmission of agmatine in brain may also be related to some CNS disorders, such as schizophrenia. Interaction of agmatine with other central neurotransmitter systems, such as the glutamatergic and nitrergic systems, seems to be very important. According to the current literature, we can expect that the central agmatinergic system may be a new key target in development of novel approaches for understanding the etiopathogenesis of CNS disorders and their treatment with drugs. The main goal of this article is to evaluate the effects of agmatine in CNS and underline its pharmacological actions in CNS and drug development

ŞİZOFRENİYİ ANLAMAKTA ALTERNATİF BİR YAKLAŞIM: NMDA RESEPTÖRLERİ ARACILIĞI İLE POLİAMİN HİPOTEZİ

The glutamate hypothesis of schizophrenia based on the observations that administration of drugs that block N-methyl-D-aspartate (NMDA) glutamate receptors could induce schizophrenia-like symptoms. There are several evidences linking abnormal glutamatergic transmission to cognitive, negative, and positive symptoms of schizophrenia and the glutamatergic system is now a major focus for the development of new compounds in schizophrenia. The polyamines are omnipresent aliphatic molecules comprising putrescine, spermidine, spermine and agmatine. The polyamines and their biosynthetic enzymes are found throughout the body, including the central nervous system (CNS), where they display specific regional distributions in the CNS. The polyamines have an important role in the modulation of cell growth and on cell membrane functions. It was hypothesized that schizophrenia may be related to a general abnormality in neuronal membranes. Agmatine, a polyamine, selectively blocks the NMDA subclass of glutamate receptors in rat hippocampal neurons. There are also several evidences indicate that a relationship between polyamines and etiopathogenesis of schizophrenia. In this review, a new approach for understanding schizophrenia via NMDA receptors and their interaction with agmatine which is a biological active polyamine transmitter in brain is proposed

Alzheimer disease and neuroplasticity: New approaches and new targets in pharmacotherapy.

Alzheimer disease (AD) is the major cause of dementia in the aged individuals. It is a neurodegenerative disorder characterized by apoptosis and loss of neurons resulting in synaptic dysfunction in central pathways involved in learning and memory. Neuroplasticity can simply be defined as changes in the brain neurons, and structural and functional changes in synapses formed by these neurons. If the changes are not confined to a single neuron but reach the level of a synapse the adaptive response formed may also be called “synaptic plasticity”. Brain is adapted to all exogenous and endogenous stimulations (i.e. environmental or emotional stresses) by neuroplasticity. The most essential statement on AD pathology is that it assault the processes associated with neuroplasticity in central nervous system (CNS). Directly focusing on the causes of damages of synaptic elements and development of new therapeutic approaches devoted to reverse impaired neuroplasticity induced by the disorder may be a more effective strategy and provide more consistent solutions in the treatment of AD. The main objective of this review article is to update our knowledge on AD in the light of the present literature and discuss the new approaches and targets such as neuroplasticity hypothesis of AD and new candidate drugs