Question regarding Benzo and Adderall interaction

[AbstractReality]

My question is regarding the duration of effects for temazepam vs its half life. For instance its duration of effects is felt roughly 5-8 hours, but remains in the blood stream any where between 8-22 hours after its effects have diminished. Now during that period a 30mg Adderal IR was consumed but its effects were greatly diminished. So is temazepam still affecting the GABA receptors well after its effects have gone?

(I meant to post this in Basic Drug Discussion)

 

[d1nach]

Most of what drugs do tend to be below our awareness. Thats why we need science.

Benzodiazepines influence gaba-a the receptors. Gaba is the primary inhibitory neurotransmitter in the brain.

Your brain has ion channels which like batteries have positive and negative charges .

Adderall is a amphetamine which acts at trace amine receptors to increase sodium dependent depolarization increasing the sensitivity of the reward centers by decreasing the amount of electrical stimulation to trigger an action potential.

Benzodiazepines long after you may feel it are still via gaba a receptors causing hyperpolarization (the opposite of depolarization) increasing the amount of electrical stimulation needed to cause a action potential of cl- ion channels

 

[AbstractReality]

So in layman terms, adderall forces the release of 3 neurotransmitters, while a benzodiazepine releases GABA which is a neurotransmitter which inhibits brain activity. Hence I should wait until the benzodiazepines is fully metabolized and out of my system for adderal to be more affective correct? I'm no neuroscientist, I just know a little bit, your reply led me on an hour of Google searching which in return I have learned a little bit more!

 

[Nagelfar]

GABAergic drugs (benzos) sedate even unto blackouts, but the monoamine system activated by adderall (amphetamine) are a euphoria mediating type of 'wakeful' stimulation, so there is a cumulative effect that ones 'slowed' conscious state from benzos with amps are more 'euphoric' in the measure of awareness. The downstream mechanism for each in its opposite pull from the other isn't a 1-to-1 cancellation, that is to say.

 

[Seppi]

Stimulants produce euphoria by stimulating the hedonic hotspots in the nucleus accumbens and ventral pallidum (this is a direct and indirect effect of their pharmacodynamics in dopaminergic neurons). Their effects on wakefulness/arousal occurs through the stimulation of the ascending reticular activating system (ARAS) (this is a direct effect of their pharmacodynamics in noradrenergic neurons). GABA is normally released from the ventrolateral preoptic area into the ARAS, which it inhibits. It also acts on other regions of the brain to promote sleep or that are involved in sleep-wake transition (e.g., on the parabrachial nucleus when released from the parafacial zone and on the lateral hypothalamus).

The direct effect of GABA in the striatum is unrelated to sleep/wakefulness because that region of the brain doesn't regulate arousal; however, GABA which is released into the striatum or onto the dopaminergic afferents to the striatum might have an indirect inhibitory effect on arousal via neural networks that connect the striatum to the ARAS.

See links on these sleep-related brain structures:
https://en.wikipedia.org/wiki/Reticular_activating_system
https://en.wikipedia.org/wiki/Lateral_hypothalamus
https://en.wikipedia.org/wiki/Ventrolateral_preoptic_nucleus
https://en.wikipedia.org/wiki/Parafacial_zone
https://en.wikipedia.org/wiki/Parabrachial_area

These are links to articles about the primary GABAergic nucleus that inhibits striatal DA projections in the VTA (and, IIRC, the substantia nigra as well) as well as the VTA dopaminergic projections to the striatum:
https://en.wikipedia.org/wiki/Rostromedial_tegmental_nucleus
https://en.wikipedia.org/wiki/Ventral_tegmental_area

 

[Nagelfar]

Stimulants produce euphoria by stimulating the hedonic hotspots in the nucleus accumbens and ventral pallidum (this is a direct and indirect effect of their pharmacodynamics in dopaminergic neurons). Their effects on wakefulness/arousal occurs through the stimulation of the ascending reticular activating system (ARAS) (this is a direct effect of their pharmacodynamics in noradrenergic neurons). GABA is normally released from the ventrolateral preoptic area into the ARAS, which it inhibits. It also acts on other regions of the brain to promote sleep or that are involved in sleep-wake transition (e.g., on the parabrachial nucleus when released from the parafacial zone and on the lateral hypothalamus).

The direct effect of GABA in the striatum is unrelated to sleep/wakefulness because that region of the brain doesn't regulate arousal; however, GABA which is released into the striatum or onto the dopaminergic afferents to the striatum might have an indirect inhibitory effect on arousal via neural networks that connect the striatum to the ARAS.

See links on these sleep-related brain structures:
https://en.wikipedia.org/wiki/Reticular_activating_system
https://en.wikipedia.org/wiki/Lateral_hypothalamus
https://en.wikipedia.org/wiki/Ventrolateral_preoptic_nucleus
https://en.wikipedia.org/wiki/Parafacial_zone
https://en.wikipedia.org/wiki/Parabrachial_area

These are links to articles about the primary GABAergic nucleus that inhibits striatal DA projections in the VTA (and, IIRC, the substantia nigra as well) as well as the VTA dopaminergic projections to the striatum:
https://en.wikipedia.org/wiki/Rostromedial_tegmental_nucleus
https://en.wikipedia.org/wiki/Ventral_tegmental_area

Seppi, are you learned enough to explain to me the specific difference between indirect monoamine agonists (transporter inhibitors & releasers; substrates and ligands to MAT and/or VMAT) and exogenous direct dopamine agonists (e.g. D2 & D3 receptor site a la *pramipexole*) with regard to the ascending reticular activating system? What is the main postulation which makes drugs of the direct-agonism class seem to give somnolence whereas indirect DAT ligands are wakeful in their subjective affect?