Is propranolol GABAergic or work on gaba receptors?

Hi, does propranolol hit gaba receptors or is it GABAergic? I'm on it and going through progesterone withdrawal, after years of being healed from benzo withdrawal. Im tapering down from 80 mgs after being prescribed it in early July. It’s been a struggle because it’s paradoxical on me. It makes my Akathisia worse. I get horrible anxiety when I cut, but made a large cut recently and felt so much better and didn’t have aka for a week, and felt better than I have in a long time since my progesterone  wd started in June. Now it’s back after I cut more yesterday. I’m down to 20 mgs. I’m praying it’s not hitting my gaba receptors or that it’s not gabaergic.

 

Thank you,

Laelani

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Pharmacodynamics

Propranolol[38]

Site Ki (nM) Species Ref

5-HT1A 55–272 Human [39][40]

5-HT1B 56–85 Rat [41][42]

5-HT1D 4,070 Pig [43]

5-HT2A 4,280 Human [44]

5-HT2B 457–513 (+)

166–316 (–) Human [45]

5-HT2C 61,700 (+)

5,010 (–)

736–2,457 Human

Human

Rodent [45]

[45]

[46][40]

5-HT3 >10,000 Human [47]

α1 ND ND ND

α2 1,297–2,789 Rat [48]

β1 0.02–2.69 Human [49][50]

β2 0.01–0.61 Human [49][50]

β3 450 Mouse [51]

D1 >10,000 Human [40]

D2 >10,000 Human [40]

H1 >10,000 Human [52]

SERT 3,700 Rat [53]

NET 5,000 (IC50) Rat [54]

DAT 29,000 (IC50) Rat [54]

VDCC >10,000 Rat [55]

Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

Propranolol is classified as a competitive non-cardioselective sympatholytic beta blocker that crosses the blood–brain barrier. It is lipid soluble and also has sodium channel blocking effects. Propranolol is a non-selective β-adrenergic receptor antagonist, or beta blocker;[56] that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β1- and β2-adrenergic receptors. It has little intrinsic sympathomimetic activity, but has strong membrane stabilizing activity (only at high blood concentrations, e.g. overdose).[57] Propranolol is able to cross the blood–brain barrier and exert effects in the central nervous system in addition to its peripheral activity.[13]

 

In addition to blockade of adrenergic receptors, propranolol has very weak inhibitory effects on the norepinephrine transporter and/or weakly stimulates norepinephrine release (i.e., the concentration of norepinephrine is increased in the synapse).[58][54] Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenoceptor activation, with the α1-adrenoceptor being particularly important for effects observed in animal models.[58][54] Therefore, it can be looked upon as a weak indirect α1-adrenoceptor agonist in addition to potent β-adrenoceptor antagonist.[58][54] In addition to its effects on the adrenergic system, there is evidence that indicates that propranolol may act as a weak antagonist of certain serotonin receptors, namely the 5-HT1A, 5-HT1B, and 5-HT2B receptors.[59][60][45] The latter may be involved in the effectiveness of propranolol in the treatment of migraine at high doses.[45]

 

Both enantiomers of propranolol have a local anesthetic (topical) effect, which is normally mediated by blockade of voltage-gated sodium channels. Studies have demonstrated propranolol's ability to block cardiac, neuronal, and skeletal voltage-gated sodium channels, accounting for its known membrane stabilizing effect and antiarrhythmic and other central nervous system effects.[61][62][63]

Pharmacodynamics

Propranolol[38]

Site Ki (nM) Species Ref

5-HT1A 55–272 Human [39][40]

5-HT1B 56–85 Rat [41][42]

5-HT1D 4,070 Pig [43]

5-HT2A 4,280 Human [44]

5-HT2B 457–513 (+)

166–316 (–) Human [45]

5-HT2C 61,700 (+)

5,010 (–)

736–2,457 Human

Human

Rodent [45]

[45]

[46][40]

5-HT3 >10,000 Human [47]

α1 ND ND ND

α2 1,297–2,789 Rat [48]

β1 0.02–2.69 Human [49][50]

β2 0.01–0.61 Human [49][50]

β3 450 Mouse [51]

D1 >10,000 Human [40]

D2 >10,000 Human [40]

H1 >10,000 Human [52]

SERT 3,700 Rat [53]

NET 5,000 (IC50) Rat [54]

DAT 29,000 (IC50) Rat [54]

VDCC >10,000 Rat [55]

Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

Propranolol is classified as a competitive non-cardioselective sympatholytic beta blocker that crosses the blood–brain barrier. It is lipid soluble and also has sodium channel blocking effects. Propranolol is a non-selective β-adrenergic receptor antagonist, or beta blocker;[56] that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β1- and β2-adrenergic receptors. It has little intrinsic sympathomimetic activity, but has strong membrane stabilizing activity (only at high blood concentrations, e.g. overdose).[57] Propranolol is able to cross the blood–brain barrier and exert effects in the central nervous system in addition to its peripheral activity.[13]

 

In addition to blockade of adrenergic receptors, propranolol has very weak inhibitory effects on the norepinephrine transporter and/or weakly stimulates norepinephrine release (i.e., the concentration of norepinephrine is increased in the synapse).[58][54] Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenoceptor activation, with the α1-adrenoceptor being particularly important for effects observed in animal models.[58][54] Therefore, it can be looked upon as a weak indirect α1-adrenoceptor agonist in addition to potent β-adrenoceptor antagonist.[58][54] In addition to its effects on the adrenergic system, there is evidence that indicates that propranolol may act as a weak antagonist of certain serotonin receptors, namely the 5-HT1A, 5-HT1B, and 5-HT2B receptors.[59][60][45] The latter may be involved in the effectiveness of propranolol in the treatment of migraine at high doses.[45]

 

Both enantiomers of propranolol have a local anesthetic (topical) effect, which is normally mediated by blockade of voltage-gated sodium channels. Studies have demonstrated propranolol's ability to block cardiac, neuronal, and skeletal voltage-gated sodium channels, accounting for its known membrane stabilizing effect and antiarrhythmic and other central nervous system effects.[61][62][63]

 

Thank you for your response aidenhome2009. So I’m assuming it doesn’t hit the gaba receptors, but I’ve read health articles that says it’s GABAergic. What does this mean? Would it make it more difficult to get off of if I’m healing from progesterone which is cross tolerant to benzos?

Anything you take to mitigate symptoms will cause a "withdrawal."  It might have some downstream effect on the GABA receptors but EVERYTHING does.  No need to obsess about if something is gabaergic or not.  No one has any idea how these drugs really affect us. What you are feeling is the rebound adrenaline from cutting the propanolol.

Anything you take to mitigate symptoms will cause a "withdrawal."  It might have some downstream effect on the GABA receptors but EVERYTHING does.  No need to obsess about if something is gabaergic or not.  No one has any idea how these drugs really affect us. What you are feeling is the rebound adrenaline from cutting the propanolol.

 

Oh I see. It’s rebound adrenaline and that’s why the anxiety is so bad? Plus I have the other withdrawal to contend with, which I’m sure is a double whammy! My mornings are especially bad. The anxiety is excruciating. Also my afternoons, when it wears off. Although it does cause me anxiety too when I take it. Is there any way to curb this type of adrenaline and anxiety while I taper & jump off? Some people don’t seem to have a problem with going off. I’m not sure if it’s covering up my progesterone withdrawal or not and that’s why I have such bad rebound anxiety.