Anxiety medications (i.e. anxiolytics) are drugs that prove safe, tolerable, and effective in clinical trials for the treatment of “anxiety” or chronic stress.
Many people derive either: (A) significant or (B) partial – therapeutic benefit from currently-available anxiolytic agents such that they help manage/reduce anxiety symptoms.
However, many individuals find that currently-available anxiolytics are problematic in one or more aspect(s):
- Side effects & long-term effects: Many anxiolytics cause unwanted side effects (e.g. sexual dysfunction, cognitive deficits, weight gain, mood changes) and long-term effects.
- Short-term efficacy: Anxiolytics such as benzodiazepines are effective over a short-term but not necessarily over a long-term.
- No therapeutic effect: Some individuals derive zero significant therapeutic benefit from currently-available anxiolytics.
- Worsening of symptoms: Others have found that currently-available anxiolytics actually worsen symptoms of their anxiety condition (e.g. exacerbation of social phobia).
Ansara (2020) report that ~50% of patients treated for generalized anxiety disorder (GAD) will not respond to first-line treatments – meaning patients desperately need new treatments. (R)
New Anxiety Medications (Clinical Trials) (2022)
What types of anxiolytics are pharmaceutical companies working on?
Clinical Trials (Phases)
If you aren’t familiar with clinical trial “phases” – it may help to read this as a basic reference so that you understand the specific phase a drug is in.
Understand that it often takes years to progress from one phase to the next – hence the slowness of drug development.
- Phase 1 (Pharmacology): Assess safety. Determine safe dosing. Identify side effects.
- Phase 2 (Exploratory): Evaluate effectiveness. Continue assessing safety.
- Phase 3 (Confirmatory): Confirm effectiveness. Monitor side effects. Compare to other treatments. Collect additional information.
- FDA approval: Treatment ruled safe and effective for mainstream use.
- Phase 4 (Post-marketing): Provide additional information after FDA approval such as risks/benefits.
I’ve sorted anxiolytics in development in order of clinical trial progress: drugs that are furthest along in clinical trials are mentioned above those that are in earlier stages of trials.
Note: I did not do any intra-phase sorting based on development progress (e.g. Phase 2A ahead of Phase 2B, etc.) – because: (A) this would’ve taken way too much time and (B) intra-phase progression isn’t really that significant.
Troriluzole (BHV-4157)
- Mechanism of action: Excitatory amino acid agonist; glutamate release inhibitor; voltage-gated sodium channel blocker
- Indication: OCD
- Developer: Biohaven Pharmaceuticals (R)
- Stage of development: Phase 3
Troriluzole (BHV-4157) is a third-generation prodrug under investigation by Biohaven Pharmaceuticals for the treatment of obsessive-compulsive disorder (OCD) – as well as spinocerebellar ataxia.
It functions primarily as a glutamate modulator wherein it: increases glutamate uptake from the synapse by augmenting the expression and function of excitatory amino acid transporters (i.e. EAAT2) positioned upon glial cells – which help clear glutamate from the synapse. (R)
It has also been shown to act as a voltage-gated sodium channel blocker.
According to some research, there’s strong evidence supporting some important perturbation of glutamate in OCD. (R)
Essentially troriluzole aims to modulate glutamatergic neurotransmission to reduce symptoms of obsessive-compulsive disorder (OCD).
Cyclobenzaprine (sublingual)
- Mechanism of action: Alpha-1 adrenergic receptor antagonist; H1R antagonist; 5-HT2AR antagonist
- Indication: PTSD
- Developer: Tonix Pharmaceuticals
- Stage of development: Phase 3
Sublingual cyclobenzaprine (TNX-102) is under investigation by Tonix Pharmaceuticals for the treatment of post-traumatic stress disorder (PTSD) – as well as fibromyalgia, agitation, alcoholism, and COVID-19 infections (among other things).
As of 2022, TNX-102 is in respective Phase 3 clinical trials for PTSD and fibromyalgia; Phase 2 clinical trials for agitation; and preclinical trials for alcoholism and COVID-19 infections.
TNX-102 will contain a “very low dose” of cyclobenzaprine that will be administered sublingually (under the tongue) – which should help provide faster and more efficient absorption with greater bioavailability relative to orally swallowed cyclobenzaprine.
Cyclobenzaprine is a centrally acting skeletal muscle relaxant with a chemical structure related to tricyclic antidepressants – and functions as an alpha-1 adrenergic receptor antagonist; H1 receptor antagonist; and 5-HT2A receptor antagonist.
A RCT of bedtime sublingual cyclobenzaprine (TNX-102 SL) reduced PTSD symptoms, improved sleep and psychosocial function, and was well tolerated – in military-related PTSD. (R)
Aloradine
- Mechanism of action: GABA-A PAM
- Indication: Social phobia
- Developer: VistaGen Therapeutics
- Stage of development: Phase 3
Aloradine (PH94B) a.k.a. Fasedienol is a drug under investigation by VistaGen Therapeutics for the treatment of social phobia and adjustment disorders.
It belongs to a class of compounds known as pherines (i.e. vomeropherines) which are odorless, synthetic, neuroactive steroids that stimulate intranasal chemosensory receptors to induce dose-dependent and reversible pharmacological effects.
This particular pherine is a positional isomer of androstadienol – an endogenous steroid/pheromone secreted by the apocrine glands.
Aloradine lacks affinity for steroid hormone receptors and instead directly activates human vomeronasal receptor cells at nanomolar concentrations.
Because aloradine is structurally similar to androstadienol, it is hypothesized to get converted into androstenol similarly – thus functioning as a GABA-A receptor positive allosteric modulator (PAM).
GABA-A receptor positive allosteric modulation enhances activity of GABA at GABA-A receptor sites – thus generating an inhibitory, anxiolytic effect – analogous to what’s observed with benzodiazepines, alcohol, anesthetics, etc. (R)
Deudextromethorphan (AVP-786)
- Mechanism of action: KATP channel inhibitor; NMDAR antagonist; NET inhibitor; SERT inhibitor; Sigma-1R agonist; Sodium channel antagonist; CYP450 enzyme inhibitor
- Indication: Agitation in AD (Fast Track)
- Developer: Avanir Pharmaceuticals (R)
- Stage of development: Phase 3
Deudextromethorphan (AVP-786) is a drug under joint development by Avanir Pharmaceuticals for the treatment of moderate-to-severe agitation in Alzheimer’s disease (a form of anxiety disorder).
Deudextromethorphan (AVP-786) is a “deuterated” form of dextromethorphan/quinidine (AVP-923) which is approved for the treatment of Pseudo-Bulbar Affect.
A deuterated drug is a small molecule in which one or more of the hydrogen atoms contained in the drug molecule have been replaced by its heavier stable isotope deuterium – which reduces metabolism and prolongs half-life.
The beneficial effects associated with deuteration of dextromethorphan/quinidine into deudextromethorphan include: reduced formation of toxic metabolites (CYP2D6 metabolism); prolonged plasma half-life; and greater brain penetration. (R)
Deudextromethorphan is thought to exert a variety of pharmacological effects including: KATP channel inhibition; NMDAR antagonism; NET inhibition; SERT inhibition; Sigma-1R agonism; sodium channel antagonism; and CYP450 enzyme inhibition. (R)
Researchers have described deudextromethorphan as a “promising treatment option for Alzheimer’s disease including agitation.” (R)
AVN-101
- Mechanism of action: 5-HT7R, 5-HT6R, 5-HT2AR, 5-HT2CR antagonist; H1R antagonist; alpha-2A/2B/2C adrenergic receptor antagonist
- Indication: Anxiety disorders
- Developer: Avineuro Pharmaceuticals
- Stage of development: Phase 2
AVN-101 is a substance under investigation by Avineuro Pharmaceuticals for the treatment of anxiety disorders. (It is also being investigated as a potential intervention for Alzheimer’s disease.)
AVN-101 is a structural analogue of latrepirdine and functions as a: 5-HT7 receptor antagonist (Ki = 153 pM); 5-HT6, 5-HT2A, 5-HT2C receptor antagonist (Ki = 1.2-2.0 nM); H1 receptor antagonist (Ki = 0.58 nM); and alpha-2A/2B/2C adrenergic receptor antagonist (Ki = 0.41-3.6 nM). (R)
For reference, latrepirdine is an antihistamine drug that has been: (A) used clinically in Russia since 1983 – and (B) evaluated in Phase 3 clinical trials for Alzheimer’s disease and Huntington’s disease – both of which failed to find any significant effect.
Latrepirdine has been shown to inhibit brain cell death in animal models of Alzheimer’s disease and Huntington’s disease and some evidence suggests it may enhance cognition in healthy individuals devoid of neurodegenerative diseases.
Phase 1 of clinical trials indicate that AVN-101 is well-tolerated at doses up to 20 mg daily and has low safety concerns.
Researchers suspect that AVN-101 may be useful for the treatment of neurodegeneration, anxiety, depression, schizophrenia, and multiple sclerosis.
It has been in Phase 2 clinical trials since 2013 – and its development seems to have stalled considering that it remains in the same clinical trial phase as of 2022.
Avineuro Pharmaceuticals planned a Phase 3 trial for AVN-101 in anxiety disorders as of December 2020 – but it’s unclear as to when Phase 3 will actually start.
Gepirone ER
- Mechanism of action: 5-HT1AR partial agonist
- Indication: Generalized anxiety disorder (GAD)
- Developer: Fabre-Kramer Pharmaceuticals
- Stage of development: Phase 2
Gepirone ER (extended-release) is a drug under investigation by Fabre-Kramer Pharmaceuticals for the treatment of generalized anxiety disorder (GAD) – as well as decreased libido.
The drug has already received FDA approval for the treatment of major depressive disorder (MDD) and is in the “preregistration” phase – so should be hitting the market soon.
Gepirone functions as a selective 5-HT1A receptor partial agonist (with unique effects on presynaptic and postsynaptic sites of 5-HT1A) – and belongs to a drug class known as “azapirones.”
Gepirone is extremely similar in its function to buspirone (i.e. Buspar), another “azapirone” drug that has been approved by the FDA since 2000 for the treatment of anxiety disorders – except gepirone is a more potent 5-HT1A agonist and interacts with D2 receptors to a significantly lesser extent (than buspirone).
It’s worth noting that gepirone is not really a “new” drug – it was first synthesized by Bristol-Myers Squibb in 1986 and purchased by Fabre-Kramer Pharmaceuticals in 1993.
A pilot study in 1987 reported that the anxiolytic effect of gepirone was “very marked” in several cases and that it has “promise as an anxiolytic agent.” (R)
An open-label study in 1993 reported that 12/17 (70.6%) of patients reported at least a 50% reduction in panic attacks within 6 weeks of gepirone administration. (R)
Unlike SSRIs which induce serotonin reuptake inhibition and cause sexual dysfunction, gepirone induces pro-sexual effects (such that it enhances sexual function or counteracts sexual dysfunction). (R)
Gepirone was reported to be safe, well-tolerated, and effective in a human randomized controlled trial (RCT) in persons with generalized anxiety disorder (GAD). (R)
Proposed “brand names” for Gepirone ER include: Travivo and Variza.
Bupropion/Dextromethorphan
- Mechanism of action: NDRI; nAChR antagonist; sigma-1R antagonist; NMDAR antagonist; SNRI
- Indication: Agitation in AD (Fast Track)
- Developer: Axsome Therapeutics
- Stage of development: Phase 2
Fixed-dose bupropion/dextromethorphan (AXS-05) is a combination drug comprised of 2 well-known drugs: (1) bupropion and (2) dextromethorphan (DXM).
It is currently under investigation by Axsome Therapeutics for the treatment of agitation in Alzheimer’s disease (a specific type of anxiety).
The mechanism of this combination drug will include: norepinephrine-dopamine reuptake inhibition & nAChR antagonism (bupropion) + sigma-1R antagonism, NMDAR antagonism, and serotonin-norepinephrine reuptake inhibition (dextromethorphan).
It has been noted that the bupropion component of this combination drug inhibits CYP2D6 enzymes in the liver to prevent dextromethorphan (DXM) breakdown into the metabolite dextrorphan (DXO) – which increases DXM to DXO ratios in the body.
My gut instinct would be that the majority of anti-agitation action from this combination drug is derived from its dextromethorphan (DXM) component – as bupropion often causes agitation as a result of its stimulatory effect involving norepinephrine/dopamine reuptake inhibition.
Still, it’s possible that individuals with Alzheimer’s disease derive substantial anxiolytic benefit from norepinephrine-dopamine reuptake inhibition and/or nAChR antagonism due to the fact that Alzheimer’s disease is associated with dysregulated/deficient norepinephrine, dopamine, and nicotinic acetylcholine receptors (nAChRs).
BI-1358894
- Mechanism of action: TRPC4 & TRPC5 inhibitor
- Indication: PTSD
- Developer: Boehringer Ingelheim
- Stage of development: Phase 2
BI-1358894 is a drug under investigation by Boehringer Ingelheim for the treatment of PTSD and panic disorder – as well as major depressive disorder and borderline personality disorder.
It functions primarily as an inhibitor of transient receptor potential canonical (TRPC) channels 4 & 5 (TRPC4 & TRPC5).
TRPC channels are widely expressed throughout the brain and involved in many aspects of brain function, but TRPC4 & TRPC5 are specifically involved in “innate fear function.” (R)
It is thought that inhibition of TRPC4 and TRPC5 channels with various drugs like BI-1358894 will attenuate “innate fear functions” and thus alleviate symptoms of panic disorder.
Several studies indicate that dual TRPC4/TRPC5 channel inhibition produces anxiolytic-like effects in mice. (R1, R2)
FKW-00GA
- Mechanism of action: 5-HT1AR partial agonist; 5-HT2AR antagonist
- Indication: GAD & Social Phobia
- Developer: Fabre-Kramer Pharmaceuticals (R)
- Stage of development: Phase 2
FKW-00GA (formerly TGW00AA) is a drug under development by Fabre-Kramer Pharmaceuticals for the treatment of generalized anxiety disorder (GAD); social phobia; and sexual function disorders.
It functions as a 5-HT1A receptor partial agonist and 5-HT2A receptor antagonist. If approved, it would be the first medication with this specific set of simultaneous actions at 5-HT1A/5-HT2A receptors.
Research suggests that 5-HT1A and 5-HT2A receptors modulate anxiety-like behavior in animal models of PTSD. (R)
The FDA approved drug buspirone functions primarily as a 5-HT1A receptor partial agonist and is effective for the treatment of anxiety plus counteracts sexual dysfunction associated with SSRIs – so this mechanism is a proven concept. (R)
Additionally, chronic administration of a 5-HT1A receptor partial agonist seems to induce hippocampal neurogenesis in rats – which could be another secondary mechanism resulting from FKW-00GA. (R)
5-HT2A receptor antagonism appears potentially useful in the treatment of insomnia and regulation of sleep – which could be beneficial among patients with anxiety. (R)
Phase 2 clinical trials have been ongoing for FKW-00GA since June 2021 for the treatment of generalized anxiety disorder; social phobia; and sexual function disorders.
JNJ-42165279
- Mechanism of action: FAAH inhibitor
- Indication: Social anxiety disorder
- Developer: Janssen R&D
- Stage of development: Phase 2
JNJ-42165279 is a drug under investigation by Janssen R&D for the treatment of social anxiety disorder – as well as pervasive child development disorders and major depressive disorder.
It functions as a potent, slowly reversible, selective inhibitor of fatty acid amide hydrolase (FAAH) enzymes.
Fatty acid amide hydrolase (FAAH) enzymes metabolize/break down fatty acid amides: anandamide (AEA); palmitoylethanolamide (PEA); and N-oleoylethanolamide (OEA).
Inhibition of FAAH enzymes causes concentrations of AEA, OEA, and PEA to significantly increase – which yield anxiolytic effects.
Research in animal models suggests that FAAH inhibitors likely modulate cannabinoid (CB1) receptors; NMDA2B receptors; and AMPA receptors – within the prefrontal cortex/amygdala to induce an anxiolytic effect. (R)
A proof-of-concept study with JNJ-42165279 (25 mg) reported anxiolytic effects in patients with social anxiety disorder relative to a placebo control. (R)
In 2016 Janssen R&D halted clinical development of JNJ-42165279 because a different FAAH inhibitor from the company Bial (BIA 10-2474) caused serious adverse events including death.
However, no serious adverse events had been reported for JNJ-42165279 and Janssen R&D eventually resumed its clinical trials in 2018.
Xenon (gas)
- Mechanism of action: NMDAR antagonist
- Indication: PTSD
- Developer: Nobilis Therapeutics
- Stage of development: Phase 2
NBTX-001 is a drug-device combination specifically designed to deliver a xenon gas mixture via a proprietary portable inhalation device (Zephryrus).
It is currently being tested by Nobilis Therapeutics for the treatment of post-traumatic stress disorder (PTSD) – as well as Parkinson’s disease.
According to Nobilis Therapeutics, xenon gas: (1) has a remarkable safety profile, (2) is already used for general anesthesia (in select cases), (3) is non-psychomimetic, non-habit forming, non-flammable, non-greenhouse gas, (4) exhibits rapid bioavailability and brain penetration. (R)
Xenon atoms interact with aromatic amino-acid residues on NMDA receptors to provide highly specific and controllable NMDA receptor antagonism.
In addition to the NMDAR antagonism, xenon appears to: (A) decrease excitatory neurotransmission via blocking AMPA, nACh (a4B2), 5-HT3, plasma membrane Ca2+ ATPase AND (B) increase inhibitory neurotransmission via stimulation of GlyR1 and TREK-1 potassium channels.
Xenon also appears to decrease proinflammatory cytokines (TNF-alpha & IL-1B), increase pro-survival factors (bcl2), and increase growth factor production (BDNF & IGF).
Preliminary research found that xenon substantially and persistently inhibits fear memory reconsolidation and reactivation and time-dependent manner – such that it could be useful in cases of PTSD. (R)
NYX-783
- Mechanism of action: NMDAR PAM
- Indication: PTSD (Fast Track)
- Developer: Aptinyx (R)
- Stage of development: Phase 2
NYX-783 is a small molecule drug under investigation by Aptinyx for the treatment of PTSD.
It functions as a NMDA receptor positive allosteric modulator (PAM) wherein it enhances the action of glutamate at NMDA receptor sites.
Research suggests that NYX-783 enhances synaptic plasticity and facilitates extinction learning in preclinical models – indicating that it could be ideal for PTSD. (R)
Thus far NYX-783 exhibits high oral bioavailability and has been well-tolerated across a wide dosing range in Phase 1 clinical trials with human subjects and has received “Fast Track” status from the FDA. (R)
SRX-246
- Mechanism of action: V1aR antagonist
- Indication: PTSD & anxiety disorders
- Developer: Azevan Pharmaceuticals
- Stage of development: Phase 2
SRX-246 is a drug under investigation by Azevan Pharmaceuticals for the treatment of post-traumatic stress disorder (PTSD) and anxiety disorders – as well as impulse control disorders.
It functions as a potent, highly-selective, orally-bioavailable vasopressin-1a receptor (V1aR) antagonist wherein it blocks activation of these receptors by the endogenous neurohormone “vasopressin.”
SRX-246 has shown effectiveness in animal models of mood disorders and Phase 1 clinical trials demonstrated excellent safety and tolerability. (R)
Evidence suggests that SRX-246 has effects on the amygdala in response to “angry face stimuli” – as well as temporoparietal junction, putamen, precuneus, and anterior cingulate. (R)
Essentially what SRX-246 did was prevented exaggerated responses to negatively valenced emotional stimuli in specific circuits associated with stress-related psychiatric disorders.
SRX-246 appears to be safe and well-tolerated in humans and reduces anxiety-potentiated startle independent of fear-potentiated startle. (R)
NMRA-511
- Mechanism of action: V1aR antagonist
- Indication: Anxiety disorders
- Developer: Neumora Therapeutics, Inc. (R)
- Stage of development: Phase 1
NMRA-511 is a small molecule under investigation by Neumora Therapeutics for the treatment of anxiety disorders.
It functions as a vasopressin-1A receptor (V1aR) antagonist (i.e. vaptan) wherein it inhibits activation of these receptor sites.
It is known that vasopressin is a neurohormone that can affect social behavior – and blocking activation of V1a receptors seems to reduce aggression in animals. (R)
A novel vasopressin-1A receptor (V1aR) antagonist known as “SRX246” appears to reduce anxiety in an experimental model in humans – specifically by decreasing anxiety-potentiated startle independent of fear-potentiated startle. (R)
NMRA-511 is in early phase development, so its efficacy hasn’t yet been evaluated in humans with anxiety disorders.
SEP-380135
- Mechanism of action: N/A
- Indication: Agitation in AD
- Developer: Sunovion Pharmaceuticals
- Stage of development: Phase 1
SEP-380135 is a drug under joint investigation by Sunovion Pharmaceuticals and Otsuka Pharmaceutical Co. for the treatment of agitation in Alzheimer’s disease (a form of anxiety).
Phase 1 clinical trials involving SEP-380135 began in May 2019, but there are zero details regarding its mechanism of action, tolerability, safety, etc. in humans.
Moreover, I was unable to find any animal model research involving SEP-380135 to suggest that it’s likely to be effective for agitation.
JNJ-61393215
- Mechanism of action: OX1R antagonist
- Indication: Panic disorder
- Developer: Janssen R&D
- Stage of development: Preclinical
JNJ-61393215 is a drug under development by Janssen R&D for the treatment of panic disorder and major depressive disorder.
Clinical trials for this compound are furthest along in major depressive disorder (Phase 2) and are in earlier phases for panic disorder (Preclinical).
JNJ-61393215 functions as a selective orexin-1 receptor (OX1R) antagonist wherein it binds to orexin-1 receptors and blocks them from being activated by the endogenous neuropeptide orexin (i.e. hypocretin).
Interestingly, long-term SSRI therapy seems to decrease CSF levels of orexin (OX) which may be a mechanism by which SSRIs treat panic disorder.
Preliminary evidence suggests that OX1Rs are involved in the pathophysiology of “panic” and that OX1R antagonism with JNJ-61393215 has potential to counteract panic responses. (R)
Neurochemical targets for new anxiolytics (Overview)
Included below is an overview of primary neurochemical targets associated with the pharmacodynamics of new anxiolytics in clinical trials.
Novel targets
These are neurochemical sites/systems that haven’t been targeted by most preexisting anxiolytic medications.
- Vasopressin-1a receptor antagonist
- Orexin-1 receptor antagonist
- FAAH inhibitor
- NMDA receptor positive allosteric modulator
- NMDA receptor antagonist
- Glutamate release inhibitor, excitatory amino acid agonist, voltage gated sodium channel blocker
- TRPC4 & TRPC5 inhibitor
- KATP channel inhibitor; NMDA receptor antagonist; NET inhibitor; SERT inhibitor; Sigma-1 agonist; Sodium channel antagonist; CYP450 inhibitor
Classic targets
These are neurochemical sites/systems that are commonly targeted by already-available anxiolytic medications.
I’m not suggesting that all mechanisms with “classic” neurochemical targets function the exact same way as already-available anxiolytics.
The specifics of action or totality of actions may differ (e.g. equal/simultaneous 5-HT1A partial agonism + 5-HT2A antagonism is said to be “first of its kind”).
I’m merely suggesting that these are not novel neurochemical targets for anxiolytics.
- GABA-A receptor positive allosteric modulator
- 5-HT1A receptor partial agonist
- Alpha-1 adrenergic receptor antagonist; H1 receptor antagonist; 5-HT2A receptor antagonist
- 5-HT1A receptor partial agonist & 5-HT2A antagonist
- NDRI; nACh receptor antagonist; Sigma-1 receptor antagonist; NMDA receptor antagonist; SNRI
- 5-HT7, 5-HT6, 5-HT2A receptor antagonist; H1 receptor antagonist; alpha-2A/2B/2C adrenergic receptor antagonist
My thoughts on new anxiolytics in development…
I’m convinced that the more safe, tolerable, and effective FDA-approved treatments for anxiety there are, the better the odds people suffering with anxiety have of finding something that works (based on their unique physiology, neurobiology, genetics, etc.).
Therefore, it’s always good to see drugs in development for the treatment of anxiety disorders.
Although it would be nice to leapfrog into the far future (~100+ years) such that all physiologic underpinnings of anxiety might be fully mapped out and treatments would be tailored to the individual based on specific neurobiological/physiological/genetic abnormalities that are causing anxiety – there’s good reason to be optimistic about anxiolytics in development.
I think several anxiolytics have potential to improve upon older anxiolytics in terms of: onset of action; effectiveness (across users & magnitude of anxiolytic effect); side effects; long-term effects; and tolerability.
To me, the most interesting anxiolytics are ones with novel neurochemical targets – because they’re at least attempting to do something different.
Continuing to essentially “spam” the market with more serotonin reuptake inhibitors; 5-HT1A receptor partial agonists; and GABA-A receptor PAMs is relatively boring – they’ll likely be about the same effectiveness/tolerability as most other drugs for anxiety.
Of all anxiolytics in development, I think ones that target NMDA receptors and/or glutamate have the most potential to improve upon existing treatments due to the fact that NMDA receptor modulation is associated with: rapid onset of action; sustained action (possibly allowing less frequent dosing); significant cascade effects (neurochemically); etc.
I’m curious about whether orexin receptor modulators will work and how they might interact with one’s circadian rhythm/behaviors.
I’m a bit concerned about potential adverse effects associated with FAAH inhibitors; TRPC4/TRPC5 inhibitors; and vasopressin-1a antagonists, but perhaps these concerns are unwarranted.
A different FAAH inhibitor trial resulted in serious adverse events/deaths; TRPC4/TRPC5 are involved in many biological processes – such that inhibition may help anxiety but cause some serious long-term effect; and although something like V1aR antagonism may reduce anxiety – it might also interfere with the ability to perceive danger or negative emotion.
Which of the anxiolytics in clinical trials are most promising?
The ones that are most promising are the ones that are furthest along in trials – it’s that simple.
Any drug can be hyped ad infinitum but the hype isn’t warranted unless it passes all phases of clinical trials… something that doesn’t make it to market is completely useless.
Which of these anxiolytics are you interested in?
- Is there a specific drug or few drugs that you’re interested in? (If so, why?)
- Which specific mechanism(s) of action are you most excited about? (Why?)
- If you’ve been in any clinical trials for these substances – feel free to share your thoughts.
- If you’re aware of any additional drugs in development for anxiety as of 2022 – mention them and I’ll add them to this list.