Conessine
Plant steroidal alkaloid, a potent histamine H3 receptor antagonist with a wakefulness-promoting profile.
Pharmacology
Contents
WHAT IS CONESSINE?
Detailed overview
Conessine is a steroidal alkaloid extracted from the bark and seeds of Holarrhena antidysenterica, a tropical shrub in the dogbane family long used in traditional medicine as an anti-dysenteric and anti-amoebic agent. Modern pharmacology rediscovered it as a potent, brain-penetrant histamine H3 receptor antagonist and inverse agonist; several medicinal-chemistry groups (Abbott, Santora and colleagues) used the natural conessine scaffold as a starting point for designing new H3 ligands. Blocking the H3 receptor releases the feedback brake on the release of histamine, acetylcholine, dopamine and norepinephrine, so it raises wakefulness and attention. It has never been tested as a cognitive enhancer in humans, so as a nootropic it is an experimental substance.
Mechanism
Histamine H3 antagonist / inverse agonist
Origin
Holarrhena antidysenterica steroidal alkaloid
Evidence
Preclinical (no human nootropic data)
Receptor profile
- Histamine H3 receptorStrong
- Alpha-adrenergic receptorsModerate
- Acetylcholine / dopamine / norepinephrine release (indirect)Moderate
Safety
Side effects, stop signs, contraindications
Side effects · 5
- No human nootropic safety data: the compound has not been tested as a cognitive enhancer in humans; effects derive from preclinical and pharmacological studies
- Insomnia or disrupted sleep with late dosing, since it is stimulating and wakefulness-promoting
- Possible rise in blood pressure and heart rate from the alpha-adrenergic and monoamine-releasing activity
- Restlessness, anxiety or tremor from the enhanced histaminergic and catecholaminergic signaling
- Unknown long-term safety; Holarrhena alkaloids carry gastrointestinal irritation potential at higher doses
Contraindications · 5
- Pregnancy and breastfeeding: safety not established, avoid
- Cardiovascular disease, arrhythmia or uncontrolled hypertension
- Anxiety disorders, panic disorder: the stimulant effect may worsen them
- Avoid combining with other stimulants or wakefulness agents due to additive effects
- Not an approved medicine; experimental research chemical, not recommended without clinical supervision
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
The alkaloid conessine and analogues as potent histamine H3 receptor antagonists
Zhao C, Sun M, Bennani YL, Gopalakrishnan SM, Witte DG, Miller TR, et al.
A new family of H3 receptor antagonists based on the natural product Conessine
Santora VJ, Covel JA, Hayashi R, Hofilena BJ, Ibarra JB, et al.
A new family of histamine H3 receptor antagonists based on a natural product: discovery, SAR, and properties of the series
Cowart M, Faghih R, Gfesser GA, et al.
Conessine, an H3 receptor antagonist, alters behavioral and neurochemical effects of ethanol in mice
Morais-Silva G, Ferreira-Santos M, Marin MT
Liquid chromatography-tandem mass spectrometry method for the quantification of a potent H3 receptor antagonist conessine in serum
Shukla M, Rajput P, Wahajuddin M
FAQ
FAQ
Plant steroidal alkaloid, a potent histamine H3 receptor antagonist with a wakefulness-promoting profile.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.