| Science |
Concept
The mechanism of action of PNB’s technology is based on the
induction of a highly selective antagonism on the 5-HT2A and
Dopamine-4 (D4) receptors in the CNS resulting in a boosting
effect on the efficacy of different psychotropics.
In antidepressants, this inhibits the specific and well-known
negative feedback loops of antidepressants leading to a faster
onset of action and a higher efficacy; in antipsychotics and anti-
parkinson drugs this will lead to a clinically significant lowering
of the burden of side effects.
Mechanism of Action in SSRI's
Selective Serotonin Re-uptake Inhibitors (SSRIs), block the
serotonin transporter responsible for pre-synaptic re-uptake of
serotonin (5-HT). Thus the availability of serotonin at the
synapse is augmented. This results not only in a therapeutic
desensitization of the post-synaptic Ser 1A (=5-HT1A) receptor,
but also an increase in the inhibition of the serotonergic neuron
via the ser2A (=5‑HT2A) receptor. This is a known negative
feedback mechanism which is believed to be (partially)
responsible for the low to moderate efficacy of SSRIs.
Figure: Action of SSRI on the serotonin release intracellular
interactions
For increase of action of SSRIs, it was postulated that 5-HT2A
antagonists would be advantageous. However, since 5-HT2A
antagonists also induce an enhanced availability of dopamine
leading to D4- receptor mediated behavioral deregulations,
highly selective 5-HT2A antagonism needs to be accompanied
by highly selective D4 antagonism.
Hence, the need for highly selective 5-HT2A / D4 antagonism to
boost anti-depressive efficacy.
Mechanism of Action in Atypical Antipsychotics (AP's)
Based on Clozapine's outstanding effectiveness it is believed
that a favourable 5HT2A/D2 receptor occupancy (RO) ratio
combined with a favourable D4/D2 receptor occupancy ratio will
lead to a best in class antipsychotic. The combination of highly
selective receptor affinity for 5-HT2A and D4 is expected to
mimic the RO profile of clozapine. As a result, PNB02 is expected
to have a comparable efficacy to Clozapine but with a lower
burden of side effects.
The mechanism of action of PNB’s technology is based on the
induction of a highly selective antagonism on the 5-HT2A and
Dopamine-4 (D4) receptors in the CNS resulting in a boosting
effect on the efficacy of different psychotropics.
In antidepressants, this inhibits the specific and well-known
negative feedback loops of antidepressants leading to a faster
onset of action and a higher efficacy; in antipsychotics and anti-
parkinson drugs this will lead to a clinically significant lowering
of the burden of side effects.
Mechanism of Action in SSRI's
Selective Serotonin Re-uptake Inhibitors (SSRIs), block the
serotonin transporter responsible for pre-synaptic re-uptake of
serotonin (5-HT). Thus the availability of serotonin at the
synapse is augmented. This results not only in a therapeutic
desensitization of the post-synaptic Ser 1A (=5-HT1A) receptor,
but also an increase in the inhibition of the serotonergic neuron
via the ser2A (=5‑HT2A) receptor. This is a known negative
feedback mechanism which is believed to be (partially)
responsible for the low to moderate efficacy of SSRIs.
Figure: Action of SSRI on the serotonin release intracellular
interactions
For increase of action of SSRIs, it was postulated that 5-HT2A
antagonists would be advantageous. However, since 5-HT2A
antagonists also induce an enhanced availability of dopamine
leading to D4- receptor mediated behavioral deregulations,
highly selective 5-HT2A antagonism needs to be accompanied
by highly selective D4 antagonism.
Hence, the need for highly selective 5-HT2A / D4 antagonism to
boost anti-depressive efficacy.
Mechanism of Action in Atypical Antipsychotics (AP's)
Based on Clozapine's outstanding effectiveness it is believed
that a favourable 5HT2A/D2 receptor occupancy (RO) ratio
combined with a favourable D4/D2 receptor occupancy ratio will
lead to a best in class antipsychotic. The combination of highly
selective receptor affinity for 5-HT2A and D4 is expected to
mimic the RO profile of clozapine. As a result, PNB02 is expected
to have a comparable efficacy to Clozapine but with a lower
burden of side effects.
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Publications
 | Overview | |
| ECNP 2011 Interaction | |
| ECNP 2011 | |
| PhaseIII_Dose_Slctn | ||
| NCDEU 2011ESR | |
| NCDEU 2011 PNB01 | |
| Pipeline | ||
| ACNP 2010 | |
| Bionity.com News | |
| EPA 2010 | |
| NCDEU 2010 | |
| SOBP 2010 | |
| ECNP 2010 | |
| Psychological Medicine | |
| News Highlights |
September 30th, 2011
First Patients Enrolled
in the PNB01 Phase
III clinical develop-
ment program in
Major Depression
August 23rd, 2011
PharmaNeuroBoost
ready to enter Phase
III development with
PNB01 in Major
Depression
First Patients Enrolled
in the PNB01 Phase
III clinical develop-
ment program in
Major Depression
August 23rd, 2011
PharmaNeuroBoost
ready to enter Phase
III development with
PNB01 in Major
Depression