I know people requested this before, sorry for being so behind. Can't find my reference list but it should be pretty easy to find stuff if you're interested (or just post/ PM me).
Agmatine
Agmatine background
Agmatine is an amine, an organic cation, and serves as an endogenous ligand at alpha 2-adrenergic and imidazoline receptors, to which it binds with high affinity. In addition, Agmatine has properties of an endogenous neurotransmitter.
Agmatine is:
(a) Locally synthesized in brain by a specific enzyme, arginine decarboxylase;
(b) Stored in a large number of neurons with selective distribution in the CNS;
(c) Associated with small vesicles in axon terminals that, at least in hippocampus, make synaptic asymmetric (excitatory) synapses on pyramidal cells;
(d) Released from synaptosomes in a Ca(2+)-dependent manner;
(e) Enzymatically degraded by agmatinase in synaptosomes
(f) Able to block the ligand-gated NMDA receptor channel at sites distinct from ligand-binding and polyamine sites.
(g) Able to competitively inhibits the activity of all isoforms of nitric oxide synthase (with exception to eNOS which we will mention later for its effects on NO production). Agmatine meets most criteria to establish it as a novel neuromodulator in the CNS (Reis, 1999).
(h) Able to activate imidazoline receptors (high affinity as an agonist; note these are downstream effects), which raises levels of beta-endorphins (leading to an increase in glucose uptake in skeletal muscle); it also lowers blood glucose levels, giving it glucose disposal agent (GDA) like properties.
Each of these points has a specific role of important in this discussion of Agmatine, indicating its vital role in the human body.
Agmatine as a neuroprotective neuromodulator
Agmatine is said to serve as an endogenous neuroprotective neuromodulator which is co-released during neurotransmitter release. It has been reported to be an endogenous neuromodulator of mental stress and has possible beneficial effects when it comes to depression, generalized anxiety, post-traumatic stress disorder, and social anxiety. Taksande et al (2009) found that that modulation of imidazoline receptors by Agmatine are implicated in the antidepressant like effect of SSRIs and may be projected as a potential therapeutic target for the treatment of depressive disorders.
Agmatine has also been indicated to be effective when it comes to pain management and palliative care.Agmatine was shown in preclinical studies to be a safe and efficacious treatment for alleviating pain and improving quality of life in lumbar disc-associated radiculopathy.
Agmatine is a specific competitive antagonist of the NMDA receptor and its guanidine moiety makes it different than traditional NMDA receptor antagonists. It’s been used many times for treating drug addictions, and another important thing to note is that Agmatine was found as an effective preventative method when it comes to glutamatergic NMDA apoptosis.
Li et al (2003) found that Agmatine reverses the NMDA-induced intracellular Ca(2+) overloading and the decrease of monoamines (including norepinephrine, epinephrine or dopamine) contents in PC12 cells, indicating that agmatine's antidepressant-like action may be related to its modulation of NMDA receptor activity and/or reversal of the decrease of monoamine contents and Ca(2+) overloading induced by NMDA. This is an important thing to keep in mind later for when we discuss the combined usage of Agmatine and D-aspartic acid (DAA) since there would appear to be a contradiction in the usage of an NMDA antagonist and an NMDA agonist (although there truly isn’t).
In hippocampal neurons Agmatine selectively modulates the NMDA subclass of glutamate receptor channels mediated by the interaction between the guanidine group and the channel pore, supporting the concept that it may serve as a neuromodulator in the brain. There is evidence that agmatine is a neuroprotective molecule and reduces excitotoxic cell death induced by glutamate or NMDA. It is possible that Agmatine, co-released with glutamate, may act to inhibit the activation of NMDA receptors during conditions leading to higher glutamate release.
Relating to bulletin points (b), (c), (d) and (f), axons that innervate pyramidal cells are glutamatergic and pyramidal cells express NMDA receptors of the glutamate subclass. It has been reported that it because of this, that agmatine may be co=stored and released with glutamate as a counter regulatory molecule as seen by electrophysiological studies of hippocampal neurons by Yang (1999).
The implication of Agmatine being co-released with glutamate release gives a clear indication for its usage when it comes to disease. It’s possible that Agmatine plays a regulatory role in normal glutamatergic neurotransmission, preventing excessive activation of NMDA receptors. The importance of this is that Agmatine is protective against ischemic injury (Gilad, 1996b), spinal cord injury (Fairbanks et al., 2000) and neuropathic pain (Fairbanks et al., 1998), conditions that arise from higher NMDA receptor activation and are reversed by NMDA receptor antagonists.
Agmatine’s effects on NO production
In the human body, there are three primary Nitric Oxide synthase pathways to be concerned with, nNOS, iNos, and eNOs. Agmatine is an inhibitor of both nNos and iNos, but importantly, it is not an inhibitor of eNos. eNos generates NO in blood vessels and is involved with regulating vascular function. eNos is associated with plasma membranes surrounding cells and the membranes of Golgi bodies within cells and is calcium current dependent. Agmatine also increases Nitric Oxide (N.O) through two pathways by stimulating the release of Nitric Oxide, while also inhibiting types of Nitric Oxide Synthase (enzymes that break down N.O.). With all of this in mind, this ultimately leads to increased NOS production, leading to an overall greater pump because Agmatine is fast acting. It’s also thought that it may be a vasodilator due to its activation of imidazoline receptors (along with its effects on eNOS).
Agmatine and D-Aspartic acid (DAA)
The important thing to distinguish here is that exogenous application of Agmatine and D-Aspartic acid work on different mechanisms for the NMDA receptor, so regardless of one being an antagonist and the other an agonist, they do not overlap. Exogenous D-aspartic acid application utilizes the R-type VGCCs and none of the others, while exogenous Agmatine is said to use the L-type VGCCs and shows no signs of inhibition of the R-type VGCCs.
Other Agmatine benefits
Agmatine can also work through stimulating the release of pituitary hormones, including Luteinizing Hormone (LH) and Growth Hormone (GH). It also increases levels of peptide Y via alpha-2-adrenoceptors within the PVN. Agmatine has a variety of benefits, and can be beneficial and desirable for athletes and bodybuilders as well as fitness enthusiasts and people in search of a healthier lifestyle as they age.
A summary of Agmatine, why you should use it and how should you use it
Agmatine is an effect supplement when it comes to pain management, neuropathic pain, ischemic injury prevention, spinal cord injury, neurotoxicity prevention, and useful for NO production, helping give you those pumps you’ve always wanted in the gym. Agmatine is also a great supplement to pair up with d-aspartic acid to help you not only feel healthier, but actually be healthier. Agmatine works through stimulating the release of pituitary hormones, including Luteinizing Hormone (LH) and Growth Hormone (GH).
Agmatine has a variety of benefits, and can be beneficial and desirable for athletes and bodybuilders as well as fitness enthusiasts and people in search of a healthier lifestyle as they age. Agmatine also increases Nitric Oxide (N.O) through two pathways – by stimulating the release of Nitric Oxide, while also inhibiting types of Nitric Oxide Synthase (enzymes that break down N.O.), and imidazoline receptor activation (blood glucose reduction + enhanced glucose intake selective to skeletal muscles). Agmatine can also be used for improved recovery, improved endurance, improved performance, improved body composition, promoting a healthy & positive mood (anti-anxiety & antidepressant properties), increased nutrient delivery to muscle cells, an enhanced insulin response, as a neuroprotective support for good health, for improved cardiovascular health, and finally, as an antioxidant.
Agmatine
Agmatine background
Agmatine is an amine, an organic cation, and serves as an endogenous ligand at alpha 2-adrenergic and imidazoline receptors, to which it binds with high affinity. In addition, Agmatine has properties of an endogenous neurotransmitter.
Agmatine is:
(a) Locally synthesized in brain by a specific enzyme, arginine decarboxylase;
(b) Stored in a large number of neurons with selective distribution in the CNS;
(c) Associated with small vesicles in axon terminals that, at least in hippocampus, make synaptic asymmetric (excitatory) synapses on pyramidal cells;
(d) Released from synaptosomes in a Ca(2+)-dependent manner;
(e) Enzymatically degraded by agmatinase in synaptosomes
(f) Able to block the ligand-gated NMDA receptor channel at sites distinct from ligand-binding and polyamine sites.
(g) Able to competitively inhibits the activity of all isoforms of nitric oxide synthase (with exception to eNOS which we will mention later for its effects on NO production). Agmatine meets most criteria to establish it as a novel neuromodulator in the CNS (Reis, 1999).
(h) Able to activate imidazoline receptors (high affinity as an agonist; note these are downstream effects), which raises levels of beta-endorphins (leading to an increase in glucose uptake in skeletal muscle); it also lowers blood glucose levels, giving it glucose disposal agent (GDA) like properties.
Each of these points has a specific role of important in this discussion of Agmatine, indicating its vital role in the human body.
Agmatine as a neuroprotective neuromodulator
Agmatine is said to serve as an endogenous neuroprotective neuromodulator which is co-released during neurotransmitter release. It has been reported to be an endogenous neuromodulator of mental stress and has possible beneficial effects when it comes to depression, generalized anxiety, post-traumatic stress disorder, and social anxiety. Taksande et al (2009) found that that modulation of imidazoline receptors by Agmatine are implicated in the antidepressant like effect of SSRIs and may be projected as a potential therapeutic target for the treatment of depressive disorders.
Agmatine has also been indicated to be effective when it comes to pain management and palliative care.Agmatine was shown in preclinical studies to be a safe and efficacious treatment for alleviating pain and improving quality of life in lumbar disc-associated radiculopathy.
Agmatine is a specific competitive antagonist of the NMDA receptor and its guanidine moiety makes it different than traditional NMDA receptor antagonists. It’s been used many times for treating drug addictions, and another important thing to note is that Agmatine was found as an effective preventative method when it comes to glutamatergic NMDA apoptosis.
Li et al (2003) found that Agmatine reverses the NMDA-induced intracellular Ca(2+) overloading and the decrease of monoamines (including norepinephrine, epinephrine or dopamine) contents in PC12 cells, indicating that agmatine's antidepressant-like action may be related to its modulation of NMDA receptor activity and/or reversal of the decrease of monoamine contents and Ca(2+) overloading induced by NMDA. This is an important thing to keep in mind later for when we discuss the combined usage of Agmatine and D-aspartic acid (DAA) since there would appear to be a contradiction in the usage of an NMDA antagonist and an NMDA agonist (although there truly isn’t).
In hippocampal neurons Agmatine selectively modulates the NMDA subclass of glutamate receptor channels mediated by the interaction between the guanidine group and the channel pore, supporting the concept that it may serve as a neuromodulator in the brain. There is evidence that agmatine is a neuroprotective molecule and reduces excitotoxic cell death induced by glutamate or NMDA. It is possible that Agmatine, co-released with glutamate, may act to inhibit the activation of NMDA receptors during conditions leading to higher glutamate release.
Relating to bulletin points (b), (c), (d) and (f), axons that innervate pyramidal cells are glutamatergic and pyramidal cells express NMDA receptors of the glutamate subclass. It has been reported that it because of this, that agmatine may be co=stored and released with glutamate as a counter regulatory molecule as seen by electrophysiological studies of hippocampal neurons by Yang (1999).
The implication of Agmatine being co-released with glutamate release gives a clear indication for its usage when it comes to disease. It’s possible that Agmatine plays a regulatory role in normal glutamatergic neurotransmission, preventing excessive activation of NMDA receptors. The importance of this is that Agmatine is protective against ischemic injury (Gilad, 1996b), spinal cord injury (Fairbanks et al., 2000) and neuropathic pain (Fairbanks et al., 1998), conditions that arise from higher NMDA receptor activation and are reversed by NMDA receptor antagonists.
Agmatine’s effects on NO production
In the human body, there are three primary Nitric Oxide synthase pathways to be concerned with, nNOS, iNos, and eNOs. Agmatine is an inhibitor of both nNos and iNos, but importantly, it is not an inhibitor of eNos. eNos generates NO in blood vessels and is involved with regulating vascular function. eNos is associated with plasma membranes surrounding cells and the membranes of Golgi bodies within cells and is calcium current dependent. Agmatine also increases Nitric Oxide (N.O) through two pathways by stimulating the release of Nitric Oxide, while also inhibiting types of Nitric Oxide Synthase (enzymes that break down N.O.). With all of this in mind, this ultimately leads to increased NOS production, leading to an overall greater pump because Agmatine is fast acting. It’s also thought that it may be a vasodilator due to its activation of imidazoline receptors (along with its effects on eNOS).
Agmatine and D-Aspartic acid (DAA)
The important thing to distinguish here is that exogenous application of Agmatine and D-Aspartic acid work on different mechanisms for the NMDA receptor, so regardless of one being an antagonist and the other an agonist, they do not overlap. Exogenous D-aspartic acid application utilizes the R-type VGCCs and none of the others, while exogenous Agmatine is said to use the L-type VGCCs and shows no signs of inhibition of the R-type VGCCs.
Other Agmatine benefits
Agmatine can also work through stimulating the release of pituitary hormones, including Luteinizing Hormone (LH) and Growth Hormone (GH). It also increases levels of peptide Y via alpha-2-adrenoceptors within the PVN. Agmatine has a variety of benefits, and can be beneficial and desirable for athletes and bodybuilders as well as fitness enthusiasts and people in search of a healthier lifestyle as they age.
A summary of Agmatine, why you should use it and how should you use it
Agmatine is an effect supplement when it comes to pain management, neuropathic pain, ischemic injury prevention, spinal cord injury, neurotoxicity prevention, and useful for NO production, helping give you those pumps you’ve always wanted in the gym. Agmatine is also a great supplement to pair up with d-aspartic acid to help you not only feel healthier, but actually be healthier. Agmatine works through stimulating the release of pituitary hormones, including Luteinizing Hormone (LH) and Growth Hormone (GH).
Agmatine has a variety of benefits, and can be beneficial and desirable for athletes and bodybuilders as well as fitness enthusiasts and people in search of a healthier lifestyle as they age. Agmatine also increases Nitric Oxide (N.O) through two pathways – by stimulating the release of Nitric Oxide, while also inhibiting types of Nitric Oxide Synthase (enzymes that break down N.O.), and imidazoline receptor activation (blood glucose reduction + enhanced glucose intake selective to skeletal muscles). Agmatine can also be used for improved recovery, improved endurance, improved performance, improved body composition, promoting a healthy & positive mood (anti-anxiety & antidepressant properties), increased nutrient delivery to muscle cells, an enhanced insulin response, as a neuroprotective support for good health, for improved cardiovascular health, and finally, as an antioxidant.