Benzoctamine

Source: Wikipedia, the free encyclopedia.
Benzoctamine
Clinical data
Trade namesTacitin
Routes of
administration		Oral, intravenous
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances)[1]
  • In general: legal
Pharmacokinetic data
Bioavailability100% for intravenous, 90% for oral
MetabolismHepatic
Elimination half-life2 to 3 hours
ExcretionRenal
Identifiers
  • N-Methyl-9,10-ethanoanthracene-9(10H)-methanamine
JSmol)
  • c1ccc3c(c1)C4c2ccccc2C3(CC4)CNC
  • InChI=1S/C18H19N/c1-19-12-18-11-10-13(14-6-2-4-8-16(14)18)15-7-3-5-9-17(15)18/h2-9,13,19H,10-12H2,1H3 checkY
  • Key:GNRXCIONJWKSEA-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Benzoctamine is a

tranquilizing. However, when co-administered with other drugs that cause respiratory depression, like morphine
, it can cause increased respiratory depression.

Medically, benzoctamine is used as a treatment for anxious outpatients to control

pharmacologic
and behavioral effects.

Animal studies have shown sedative hypnotic drugs tend to show dependency in animals, but benzoctamine has been shown to not be addictive. Other animal studies also point to the drug as a possible mechanism by which to reduce blood pressure through the adrenergic system.

Chemically, benzoctamine belongs to the class of compounds called dibenzobicyclo-octadienes. It is a tetracyclic compound, consisting of four rings in a three dimensional configuration, and is very closely related structurally to the tetracyclic antidepressant (TeCA) maprotiline, differing only in the length of their side chain.

Medical uses

Anxiety

Benzoctamine's main clinical use is for the treatment of

psychoneurosis, a daily dosage of 30 to 80mg of benzoctamine was shown to be just as effective as 6–20mg of diazepam.[5] In another study one group of patients were given 10mg of benzoctamine three times a day, while another group was given 5mg of diazepam, and the treatments were equivalent.[5] While these studies point to higher doses of benzoctamine being needed to exert the same pharmacological effects, the drug is still popular because of its ability to act as an anxiolytic without producing the common respiratory depression associated with other sedative drugs. Some studies have even shown that it stimulates the respiratory system.[6]

Benzoctamine and sodium amylobarbitone

In a study used to compare benzoctamine to

sodium amylobarbitone as a sleep promoter, it was found that during administration of both drugs, patients reported that their sleep was less restless, and drowsiness was diminished.[7] The study further showed that while sodium amylobarbitone caused withdrawal rebound symptoms, benzoctamine did not.[7] It was also found that benzoctamine reduced plasma corticosteroid hormone levels.[7] There is a relationship between anxiety and adreno-corticosteroid activity, with raised levels commonly being reported as an indication of stress.[7] The study showed that benzoctamine, a drug reported to reduce anxiety, was also able to reduce the hormones that potentially cause it.[7]
This points to a phenomenon often seen within pharmacology where drugs intended for other uses often have far-reaching and rarely considered effects.

Benzoctamine vs. chlordiazepoxide in anxiety neurosis

Benzoctamine has been found to have the same efficacy as chlordiazepoxide when treating anxiety neurosis.[8]

Sleep sedation

While benzoctamine was made to be an alternative to the

carbon dioxide partial pressure PCO2.[9] This confirmed previous statements that claimed the drug did not cause respiratory failure. The main goal of this clinical study was to confirm the findings of another study that showed benzoctamine did not reduce CO2 responsiveness, but instead increased the ventilatory response to CO2.[10]

There are usually many risks associated with using sedatives on patients who are suffering from respiratory failure, which has made it difficult to administer tranquillizing medications in situations when they are desirable. It is not known why this drug is safe and its benzodiazepine cousins are not, but a possible explanation for this phenomenon might come from its similarity in structure to

tricyclic antidepressants, which have also been shown to not cause respiratory failure.[9]
While further experimentation is necessary, this study points to benzoctamine's possible consideration for sedation in respiratory failure patients.

Other uses

Hypertension

A possible treatment for

serotonin antagonism was not sufficient to reduce blood pressure by using the highly selective serotonin antagonist 1-(1-naphthyl)-piperazine, which was not able to decrease the blood pressure of the rats.[11]
These studies have yet to be repeated in humans.

Side effects

Common side effects

Common side effects include drowsiness, dry mouth, headache, and dizziness.

Serotonin turnover

Studies have shown that benzoctamine increases level of serotonin.[12] Scientists confirmed these results and proposed that the method of action was inhibition of serotonin uptake since the drug also blocked the serotonin depleting action of extra-neuronal monoamine transporters (EMT).[13] This would lead to increased stimulation of serotonin receptors through a negative feed back mechanism, eventually decreasing serotonin out put. However, the study points out that other studies have shown that drugs combined with EMT cause a lowering of body temperature that in fact results in a decrease in 5HT turnover.[13] This means that body temperature effects cannot be ruled out.

Pharmacology

Not much is understood about how benzoctamine produces its anti-anxiety effects, but rat studies have shown that the possible mechanism of action is by way of increased turnover of catecholamines.[14] In addition to serotonin it has also been shown to decrease epinephrine, dopamine, and norepinephrine turnover by antagonizing their receptors.[13] When given intravenously in doses of 20–40mg there are no significant differences in efficacy.[15] Oral doses exceeding 10mg three times daily do not increase the effects of the drug.[5] Assuming serotonin postsynaptic antagonism is the main mechanism by which benzoctamine carries out its effects, studies have shown it to have an IC50 value of 115 mM at the serotonin receptor.[16]

Pharmacokinetics

Benzoctamine can be injected directly into the blood or given as tablets. When given as tablets, it is given in doses of 10mg three times daily.[5] And when given intravenously, patients are given the drug at a rate of 5mg/minute until 20–40mg of drug has been injected.[15] Benzoctamine can be analyzed as the 3H acetyl derivative and N-methyl metabolite it gets broken down into using radioactive analysis.[17] Benzoctamine has a half-life of 2–3 hours,[6] with a bioavailability of 100% when given intravenously and around > 90% when given orally.[18] The average time to achieve peak plasma concentrations is 1 hour[6] and the volume of distribution for a 70kg person is 1-2 L/kg.[6]

See also

References

  1. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ISSN 0300-0605
    .
  3. ^ Robson WL (2022-05-19). Cendron M (ed.). "Enuresis Treatment & Management: Approach Considerations, Initial Management, Alarm Therapy". MedScape.
  4. ^ a b c "Welcome to Hodoodo Chemicals". www.hodoodo.com. Retrieved 2024-02-09.
  5. ^
    S2CID 44552044
    .
  6. ^
    S2CID 39957236
    .
  7. ^
    PMID 4349414
    .
  8. PMID 4566124
    .
  9. ^
    PMID 20791872
    .
  10. ^ Geisler L, Rost HD (1970). Respiratory stimulation. Proceedings of International Symposium on Anxiety and Tension-New Therapeutic Aspects. St. Moritz. p. 57.
  11. ^
    PMID 6311738
    .
  12. ^ "Benzoctamine". go.drugbank.com. Retrieved 2024-02-09.
  13. ^
    PMID 4480288
    .
  14. PMID 5512696
    .
  15. ^
    S2CID 221427437
    .
  16. PMID 2550260
    .
  17. PMID 8527998
    .
  18. ISBN 0-443-07145-4
    .
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