Depressant
Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include facilitation of GABA and inhibition of glutamatergic or monoaminergic activity.
Barbiturates are sometimes used recreationally; they cause dependence and severe withdrawal, and they have a high risk of fatal overdose due to respiratory depression.
Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties.
High doses of shorter-acting benzodiazepines induce anterograde amnesia, which may be helpful for surgical and procedural anesthesia to reduce patient recall.
These properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal, and as a premedication for medical or dental procedures.
[4][5] The chemical compound tetrahydrocannabinol (THC), which is found in cannabis, has many depressant effects, such as muscle relaxation, sedation, decreased alertness, and tiredness.
Discontinuation symptoms include confusion, disorientation, delirium, hallucinations (auditory and visual), insomnia, decreased appetite, anxiety, psychomotor agitation, pressured speech, tremor, tachycardia, and seizures, which could be fatal.
While their popularity has gradually waned due to concerns over overdose and dependence potential, newer derivatives of carbamates continue to be developed.
Not approved: Gabapentinoids are a unique and relatively novel class of depressants that selectively bind to the auxiliary α2δ subunit (CACNA2D1 and CACNA2D2) site of certain VDCCs and thereby act as inhibitors of α2δ subunit-containing voltage-gated calcium channels.
α2δ is located on presynaptic neurons and affects calcium channel trafficking and kinetics, initiates extracellular signaling cascades and gene expression, and promotes excitatory synaptogenesis through thrombospondin 1.
Ziconotide, a non-gabapentinoid ω-conotoxin peptide, binds to the N-type calcium channels and has analgesic effects 1000 times stronger than morphine.
They act on the α2δ site to lower the release of many excitatory and pro-nociceptive neurochemicals, including glutamate, substance P, calcitonin gene-related peptide (CGRP), and more.
They are also used for postherpetic neuralgia, neuropathic pain associated with diabetic neuropathy, fibromyalgia, generalized anxiety disorder, and restless legs syndrome.
Baclofen is primarily used for the treatment of spastic movement disorders, especially in instances of spinal cord injury, cerebral palsy, and multiple sclerosis.
Reuters reported on 25 March 2010 that "Pfizer Inc violated a United States racketeering law by improperly promoting the epilepsy drug Neurontin (gabapentin).
The case stems from a claim from Kaiser Foundation Health Plan Inc. that "it was misled into believing Neurontin was effective for off-label treatment of migraines, bipolar disorder and other conditions.
[53][54][55][56] Common side effects of gabapentinoids include drowsiness, dizziness, weakness, increased appetite, urinary retention, shortness of breath, involuntary eye movements (nystagmus), memory issues, uncontrollable jerking motions, auditory hallucinations, erectile dysfunction, and myoclonic seizures.
Both Xywav and Xyrem are Schedule III[103][104] and have a black box warning[105] for central nervous system depressant effects (hypoventilation and bradycardia) and for their very high potential for abuse.
[123] Symptoms include delirium, tremor, anxiety, tachycardia, insomnia, hypertension, confusion, sweating, severe agitation which may require restraint,[124] auditory and visual hallucinations, and possibly death from tonic-clonic seizures.
The midbrain nuclei of the brain stem, with structures like the periaqueductal gray, reticular formation, and rostromedial tegmental nucleus, are responsible for the majority of the physical and psychological effects of endogenous and exogenous opioids.
The nociception opioid peptide receptor (NOP) is involved in the regulation of numerous brain activities, particularly instinctive emotional behaviors and pain.
[147] A person overdosing on opioids or opiates is presented with respiratory depression, a lethal condition that can cause hypoxia from slow and shallow breathing.
The brain stem no longer detects carbon dioxide in the blood, so it does not initiate the inhalation reflex, usually resulting in hypoxia.
The drug increases inhibitory GABAergic tone and causes neuro-inhibition of the cortical and limbic systems, observed clinically as a sedative-hypnotic effect.
Infants born to mothers addicted to glutethimide responded well initially, then had a recurrence of symptoms about 5 days later, including overactivity, restlessness, tremors, hyperreflexia, hypotonia, vasomotor instability, incessant crying, and general irritability.
It usually consists of restlessness, nausea and vomiting, decreased appetite, tachycardia, insomnia, tremor, hallucinations, delirium, confusion, and seizures; and, which are possibly fatal: EEG photoparoxysmal response, myoclonic twitches, fever, muscle spasms, and irritability.
[164] Methaqualone was first synthesized in India in 1951 by Indra Kishore Kacker and Syed Husain Zaheer, who were conducting research on finding new antimalarial medications.
[citation needed] Large doses of methaqualone can cause euphoria, disinhibition, increased sexuality and sociability, muscle relaxation, anxiolysis, and sedation.
Diproqualone is the only analogue of methaqualone that is still in widespread clinical use due to its useful anti-inflammatory and analgesic effects, along with the sedative and anxiolytic actions common to other drugs of this class.
There are still some concerns about the potential of diproqualone for abuse and overdose; it is sold not as a pure drug but as the camphosulfonate salt in combination mixtures with other medicines such as ethenzamide.
