autonomic nervous system: nootropics and compounds | sci-wiki

Tofisopam

Tofisopam is an anxiolytic drug of the 2,3-benzodiazepine class, marketed in parts of Europe and Asia under brand names such as Grandaxin [1]. Unlike the familiar 1,4-benzodiazepines such as diazepam, it relieves anxiety without producing sedation, muscle relaxation, memory impairment, or anticonvulsant effects [2]. It is used mainly for anxiety and autonomic symptoms, and it is not approved in the United States or Canada.

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Neurosteroid

Androstadienone

Androstadienone (androsta-4,16-dien-3-one) is an endogenous volatile C19 16-androstene steroid found in male axillary sweat, semen, saliva and plasma, and the most intensively studied candidate human chemosignal or "pheromone." It is not a classical ion-channel neurosteroid; its central actions are triggered peripherally through the main olfactory epithelium, where the odorant receptor OR7D4 (a G-protein-coupled receptor) is the principal transducer and its genetic variation explains much of the wide person-to-person difference in whether the compound smells sweaty, urinous, sweet or nothing at all. Controlled exposure has been reported to modulate mood, sustained attention, salivary cortisol, autonomic tone and hypothalamic and frontolimbic activity, often in a sex-dependent and strongly context-dependent way. The evidence base is large but contested; effect sizes are small and several findings have failed to replicate, so the compound remains a putative rather than a proven pheromone.

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Neurosteroid

Estratetraenol

Estratetraenol (estra-1,3,5(10),16-tetraen-3-ol) is an endogenous estrane steroid (a C18 steroid built on the same carbon skeleton as the estrogens) first isolated from the urine of pregnant women in 1968. It carries an aromatic A-ring like the classical estrogens but lacks the oxygen at carbon 17, which leaves it essentially devoid of conventional estrogenic hormone activity. It is best known as a putative human chemosignal (a chemical thought to carry social information between individuals), where it is treated as the female-associated counterpart to the male-associated steroid androstadienone. A body of psychophysical and neuroimaging work reports that trace, near-odorless exposure to estratetraenol can bias perception, mood, and physiological arousal in a sexually dimorphic manner, although independent replications have been mixed and its status as a true pheromone remains contested.

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Anxiolytic

Fasedienol

Fasedienol (developmental code PH94B; international nonproprietary name aloradine) is a synthetic steroidal compound of the "pherine" class, formulated as a low-dose intranasal spray for the acute, as-needed treatment of anxiety. It is chemically the synthetic 4,16-androstadien-3β-ol isomer (molecular formula C19H28O), structurally related to but deliberately distinct from the endogenous putative human pheromone 5,16-androstadienol. Unlike classical neurosteroids such as allopregnanolone, it is not appreciably absorbed into the systemic circulation and does not act by directly modulating central GABA-A receptors (the brain's main inhibitory ion channels); instead it activates peripheral chemosensory neurons in the nasal mucosa, generating afferent signals that reach the olfactory bulb and amygdala (the brain's fear and threat-processing hub). Developed by Pherin Pharmaceuticals and later licensed to VistaGen Therapeutics, it advanced through positive Phase 2 trials in social anxiety disorder but produced mixed results in the pivotal PALISADE Phase 3 program, and it has continued to be investigated for generalized anxiety disorder and post-traumatic stress disorder.

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