I found this:
Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA); however, it does not directly bind to GABA receptors. Pregabalin binds to the alpha
2-delta site of voltage-gated calcium channels in the central nervous system (CNS) tissues.
4
This calcium channel modulation may reduce the release of many neurotransmitters.
4
Like gabapentin, the precise mechanism of action of pregabalin is unknown.
4 However, gabapentin differs from pregabalin because of the reduced binding affinity to voltage-gated calcium channels.
6 Pregabalin is six-times more potent than gabapentin in binding affinity to the alpha
2-delta voltage-gated calcium channel.
9 The manufacturer states that 50 mg of pregabalin is approximately equal to 300 mg of gabapentin. This alteration of calcium channel function is not to be confused with calcium-channel blockers. Pregabalin and gabapentin alter channel function without complete blockade of the calcium channel resulting in virtually no change in systemic blood pressure or coronary blood flow changes.
And also this:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465829/
[h=1]Comparative effects of chronic administrations of gabapentin, pregabalin and baclofen on rat memory using object recognition test[/h]
Asma Salimzade,
Ali Hosseini-Sharifabad, and
Mohammad Rabbani*
Author information Article notes Copyright and License information Disclaimer
Go to:
[h=2]Abstract[/h]Memory impairment is one of the greatest concerns when it comes to long-term CNS-affecting drug administration. Drugs like gabapentin, pregabalin and baclofen are administered in a long-term period in conditions such as epilepsy, neuropathic pain, spasticity associated with spinal cord injury or multiple sclerosis. Despite their wide spread use, few data are available on the effects of these drugs on cognitive functions, such as learning memory. In the present study, the effects of long-term administration of gabapentin, pregabalin and baclofen on memory were investigated in a comparative manner. Male Wistar rats received intraperitoneal (i.p.) injection of gabapentin (30 mg/kg), pregabalin (30 mg/kg), baclofen (3 mg/kg), combination of gabapentin/baclofen (30/3 mg/kg) and combination of pregabalin/baclofen (30/3 mg/kg) once a day for 3 weeks respective to their groups. After the end of treatments, rat memories were assessed using the object-recognition task. The discrimination and recognition indices (RI and DI) in the T2 trials were used as the memory indicating factors. The results showed that daily i.p. administrations of pregabalin but not gabapentin or baclofen significantly decreased DI and RI compared to saline group. In combination groups, either gabapentin or pregabalin impaired discrimination between new and familiar objects. Our findings suggested that pregabalin alone or in combination with baclofen significantly caused cognitive deficits.
Keywords: Gabapentin, Pregabalin, Baclofen, Object recognition task, Memory, Chronic
Go to:
[h=2]INTRODUCTION[/h]Neuropathic pain (NP) is a pain incepted or caused by a primary disease, lesion or dysfunction in the nervous system (
1). It has varied causes such as spinal cord injury, stroke, multiple sclerosis, diabetes mellitus, neoplasia tumors and other diseases affecting the CNS (
1,
2). Neuropathic pain thus affects a large number of patients worldwide and often it has a significant impact on the quality of life (
3,
4). In patients with upper motor neuron disease, persistent pain can be associated with spasticity (
5). Antiepileptic drugs are used for treating epilepsy, but have also been used for treating neuropathic pain (
6). Baclofen is a muscle relaxant and an antispastic agent. It is used to treat spasms, pain, and stiffness (
7,
8). Antiepileptic drugs work in a number of different ways, all of which have relevance to their effect on pain. Gabapentin is an antiepileptic drug that, despite its name, has no interaction with GABA receptors or GABA metabolism (
9). It appears to have an inhibitory action at voltage-gated calcium channels (VGCCs) and also disrupt an entire series of N-methyl-D-aspartate (NMDA)- activated events involved in central sensitization (
10,
11). Pregabalin is a more recently developed drug that (like gabapentin) is licensed for the treatment of peripheral neuropathic pain. It acts on the VGCCs too, although its pharmacokinetic properties are not identical to those of gabapentin (
12,
13). Baclofen is a GABA
B receptor agonist that is mainly used for the treatment of spasticity (
7). Baclofen is postulated to block mono-and- polysynaptic reflexes by acting as an inhibitory neurotransmitter, blocking the release of excitatory transmitters. Baclofen also has been found to block VGCCs (
14,
15).
Pharmacological interference has the potential to disrupt normal neurotransmission in areas of the brain responsible for cognitive functions. Antiepileptic drugs can adversely affect cognitive function by suppressing neuronal excitability or enhancing inhibitory neurotransmission (
16). On the other hand, there is extensive evidence indicating that the administration of GABAergic drugs can cause cognitive deficits but very few studies have addressed this issue (
17). The object recognition task (ORT) is used to evaluate cognition, particularly recognition memory, in rodent models of CNS disorders. This test is based on the spontaneous tendency of rodents to spend more time exploring a novel object than a familiar one. The choice to explore the novel object reflects the use of learning and recognition memory. Antiepileptic drugs such as gabapentin and pregabalin and other adjuvant drugs like baclofen are increasingly used in treatment of neuropathic pain. Because of the side effects of long-term treatment with these drugs, we decided to evaluate the chronic effect of gabapentin, pregabalin and baclofen alone and in combination on rat memory using ORT. The data of this study was compared with scopolamine that induces memory deficits in ORT model (
18).
[h=2]DISCUSSION[/h]There are extensive evidences indicating that the administration of GABAergic drugs affects memory retention and learning. It has been shown that GABA receptor agonists impair memory and antagonists facilitate memory (
24). Antiepileptic drugs can adversely affect cognitive function by suppressing neuronal excitability or enhancing inhibitory neurotransmission (
25). Cognitive effects of gabapentin and other antiepileptic drugs have been compared in a number of clinical studies. Leach,
et al. studied gabapentin in 27 patients in an add-on polytherapy study after 4 weeks of adjunctive therapy and found no change in psychomotor and memory tests. Drowsiness was more often found in higher dosing (2400 mg) (
26). Mortimore,
et al. did not find a difference between continued polytherapy or an add-on with gabapentin in measures of quality of life (
27). Martin,
et al. used an acute dose and rapid titration in 6 volunteers and did not find cognitive effects of gabapentin (
28). In a small randomized double blind placebo controlled crossover study that was done in healthy volunteers that were treated by single low dosages (50-400 mg) of gabapentin showed a subtle positive psychotropic effects (e.g. improved concentration and attention) (
29). Gabapentin acutely harms neuronal pathway via adjustment of the mechanism of neuronal cognitive pathway in different steps of learning tasks (
30).
Then theres some links that might be helpful:
[h=1]Neuropsychological and psychiatric impact of add-on titration of pregabalin versus levetiracetam: A comparative short-term study[/h]
https://www.sciencedirect.com/science/article/pii/S1525505006002757
[h=1]Cognitive effects of pregabalin in healthy volunteers[/h]http://n.neurology.org/content/74/9/755.short
I know im probably not really helping in answering your question. but perhaps the ansers can be hashed out from the right studies and comparisons. I take a lot of gabapentin so i want to dig thru the literature to im realizing i havent in a while and now i have a different angle. thanks