Classes of Peptides - Neurotransmitter inhibitor peptides
Jul 27, 2017
Our second class of peptides are Neuropeptides.....
Neurotransmitter inhibitor peptides inhibit acetylcholine release at the neuromuscular junction. Seven types (A–G) of botulinum toxin target peripheral cholinergic neurons where they selectively proteolyse synaptosome- associated protein of 25 000 Da (SNAP-25), syntaxin 1 and synaptobrevin, the soluble N-ethyl- maleimide-sensitive factor attachment protein receptor (SNARE) proteins responsible for transmitter release, to cause neuromuscular paralysis but of different durations. Type A toxin proteolytically degrades the SNAP-25 protein, a type of SNARE protein. The SNAP-25 protein is required for the release of neurotransmitters from the axon endings. Botulinum toxin specifically cleaves these SNAREs, and so prevents neurosecretory vesicles from docking and or fusing with the nerve synapse plasma membrane and releasing their neurotransmitters. botulinum toxin type A (BXT-A) paralysis lasts longer (4–6 months) among botulinum toxin subtypes, make it a good choice for anti-wrinkle uses.
The neurotransmitter-affecting peptides currently incorporated into cosmeceutical products were developed as topical mimics of the botulinum neurotoxins. All botulinum neurotoxin serotypes are single-chain polypeptides which inhibit acetylcholine release the at the neuromuscular junction in a three step process. The single chain polypeptides are activated by proteases and bind to a receptor on the presynaptic nerve terminal, which enable internalization of the bound toxin into the cell. It prevents the release of acetylchonline.
Use of polypeptides inhibits the repetitive contraction of the intrinsic muscles of facial expression and thereby reduces lines. They work by raising the threshold for minimal muscle activity, requiring more signal to achieve movement and reducing subconscious muscle movement over time.
Most of these peptides act on the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex, whereas others target different parts of the neuromuscular junction.
Examples are Agireline (Acetyl hexapeptide-3).
Argireline is a synthetic peptide that is especially marketed as a component of eye care products and patterned from the N-terminal end of the protein SNAP-25 that inhibits SNARE complex formation and catecholamine release. Inhibition of noradrenaline and adrenaline release was also demonstrated. Argireline inhibits vesicle docking by preventing the tertiary SNARE complex formation, which is involved in synaptic vesicle exocytosis. A 5% cream applied twice daily demonstrated a 27% decrease in periorbital rhytids after 30 days.
The clinical results of this peptide's inhibitory effect on neurotransmitter release may raise the threshold for minimal muscle activity, requiring more signal to achieve movement and thus reducing subconscious muscle movement over time. If delivered to targeted facial muscles, there could be a decrease in dynamic facial lines and wrinkles. Several other peptides have been formulated which act on different parts of the neuromuscular junction or affect certain neurotransmitters.
Another open label vehicle-controlled trial, 10% acetyl hexapeptide-3 and placebo creams were applied twice daily on 10 women and demonstrated a nearly 30% vs. 10% improvement in periorbital rhytids after 30 days as measured by silicone replica analysis respectively.
Pentapeptide-3 (Vialox) acts similarly to turbocurarine, the main active ingredient of curare. The peptides is a competitive antagonist at the acetylcholine postnaptic membrane receptor. As the acetylcholine receptors are blocked, the sodium ion channel remains closed. Therefore there is no sodium ion influx to depolarize the cell and lea to muscle contraction, and smooth muscles stay relaxed.
Luphasyl another pentaptide modulates calcium channels by mimicking enkephalins. Enkephalins are endogenous opioids that inhibit neuronal activity. Their receptors are on the outside of neurons, coupled to inhibitory G-proteins. The proteins close calcium ion channels and open potassium ion channels. Preventing the entry of calcium ions into the neuron avoids vesicle fusion and consequently inhibits acetylcholine release across the synapse to the muscle. This diminishes muscle contraction.An active-controlled trial, compared cream containing 5% leuphasyl solution (0.05%), cream containing 5% Argireline solution (0.05%) and combination. Mean wrinkle reductions were 11.64% vs. 16.26% vs. 24.62% for Leuphasyl, Argireline and combination respectively. This study suggested a synergistic effect between Leuphasyl and Argireline.
Pentapeptide-3 (Vialox), a synthetic peptide that is a competitive antagonist at the acetylcholine receptors, safely blocks the sodium ion release at the synaptic membrane on muscles so they can- not contract as frequently. In vitro tests showed muscle contractions reduced by 71% within 1 min after treatment and 58% 2 h later. Less frequent muscle contractions result in shallower lines. After 28 days of twice-daily use, wrinkle depth was reduced 49%.
Pentapeptide-3 (Vialox), a synthetic peptide that is a competitive antagonist at the acetylcholine receptors, safely blocks the sodium ion release at the synaptic membrane on muscles, so they cannot contract as frequently. In vitro tests showed muscle contractions reduced by 71% within 1 min after treatment and 58% 2 h later. Less frequent muscle contractions result in shallower lines. After 28 days of twice-daily use, wrinkle depth was re- duced 49%.
Synake acts similarly to Walglerin-1. Walglerin-1 is a neurotoxin found in the venom of the temple viper, which causes reversible antagonism of muscular nicotinic acetylcholine receptors at the postsynaptic membrane. It prevents binding of acetylcholine to the receptor, preventing it from from opening. In the closed state, there is no uptake of sodium ions so that no depolarization takes place and the muscles remain relaxed.
Acetyl octapeptide-3 (SNAP-8) is an elongated form of Argireline with similar effect. It mimics SNAP-25 N-terminal end and competes with it. A cream containing 10% SNAP-8 solution was applied to periorbital area twice daily for 4 weeks. Mean wrinkle reduction after 28 days was 34.98%.
Inhibitor peptides provide viable alternatives for wrinkle reduction, especially around the periorbital area for those who wish to avoid the botulinum toxin. Unlike botox, they do not have the effect of muscle paralysis and wasting.
About the Author
Jacine Greenwood is an internationally recognised educator who is known within the industry for her up to date knowledge and her ability to deliver training in an easy to understand method.
Jacine is a Cosmetic Chemist as well as Esthetician. Jacine holds 6 Diplomas and a Bachelor of Nursing and her knowledge is well respected by her peers. With over 21 years experience in the industry and a background of cosmetic formulation, Jacine has an immense knowledge of current trends in research and new developments in the industry.
Jacine has been continually educating herself in all aspects of skin function and cosmetic chemistry for the past 21 years. Jacine’s knowledge is current and has a vast knowledge of the active ingredients that are being released onto the market.
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