Life extending properties of BBP750 in Caenorhabditis elegans

Lam Hoi-ka, E. ten Winkel, bbPharma

Certain drugs such as mianserin have been reported to extend the lifespan in worms by 30%. We have tested BBP750 a serotonin modulator with octopamine inhibiting effects.
Caenorhabditis elegans on BBP750 enhanced diet showed a 25% boost in lifespan compared to C. elegans on a regular diet (bacterial lawn grown on an agar plate, with and without BBP750 enrichment). No Dauer stadia were seen

Interestingly, effects from other studies on BBP750 show that rats have slightly decreased food-intake compared to rats on a regular diet.

Conotoxin in pain transmission

Pritsana Khamchaew, Edwin ten Winkel, bbPharma

In the vertebrate nervous system the calcium influx in the pre-synaptic end of the nerve fiber leads to a release of neurotransmitter in the synaptic cleft. Specific ion channels facilitate the calcium influx and the synaptic signal transmission.
The conopeptide reversibly antagonises -highly specifically- a special type of calcium channel (the N-Type), that can be found in a high density in the Central Nervous System and that is responsible for pain transmission.
Our conotoxin, a nerve agent, binds to and blocks these N-Type calcium channels and thus blocks the release of neurotransmitter. The nerve impuls is thus interrupted pre-synaptically. This effect -in contrast to morphine- is immediate and complete.

Normalisation of CD4 count in an individual with HIV

Pritsana Khamchaew, Edwin ten Winkel, bbPharma

A 35 year old Chino-Thai male with previously diagnosed HIV and onset of AIDS was included in a clinical trial investigating effect of BBP153 on CD4 count in patients with HIV. Baseline value upon entry of the trial for this patient was 221 CD4 cells/mm3. He received 1 gram of BBP153 daily. CD4 count was repeated after 8 weeks and 912 CD4 cells/mm3 were found while symptoms were cleared. Normal CD4 values in Caucasians are reported to be 500-1500 cells/mm³¹, whereas for Ethnical Chinese, sometimes lower normal values are reported (727 ± 255 cells/μl). These results are promising but a full analysis of the trial needs to be made.

12 December 2008. The man remains to be symptom free and has normalized CD4 count

1. Normal Values for CD4 and CD8 Lymphocyte Subsets in Healthy Chinese Adults from Shanghai
Weiming Jiang, Laiyi Kang, Hong-Zhou Lu, Xiaozhang Pan, Qingneng Lin, Qichao Pan, Yile Xue, Xinhua Weng, and Yi-Wei Tang

Effects of Coccinia indica and tolbutamide on human bloodsuger values

Pritsana Khamchaew, Edwin ten Winkel, bbPharma

Abstract. Coccinia indica (Climbing ivy gourd) is a herb used in traditional and Ayurvedic medicine in India where it is often combined with Abroma augusta.

100 patients with confirmed type II Diabetes mellitus were rondomized over two groups. One group received 2dd 200mg/kg of Coccinia indica (in watery extract, freeze dried and encapsulated), wheras the other group recieved Tolbutamide 2dd 200mg/kg. Treatment results were determined after 45 days.

Both Coccinia Indica and Tolbutamide caused a statistical and clinically significant lowering of bloodsuger values in comparison to base values. There were no statistically significant differences between patients treated with Coccinia Indica and patients treated with tolbutamide.

In vivo activity of NNRTI BBP153 against wildtype HIV-1

Pritsana Khamchaew, Edwin ten Winkel, bbPharma
BBP153, is shown to have potent in vitro activity, high genetic barrier to resistance development and favorable pharmacokinetics.

In Vitro Activity
BBP153, a new NNRTI, exhibits potent in vitro anti-HIV activity with an EC₅₀ against wild-type HIV-1 of 0.5 nM, and little or no loss of activity against HIV-1 variants having key NNRTI resistance mutations.

This might be a result of the adaptability of the interaction between BBP153 and the NNRTI binding site of HIV-1 reverse transcriptase which allows the compound to bind in different modes and adjust in case of RT mutations.

Male preputium eversion in Biomphalaria straminea caused by fluoxetine

Lam Hoi-ka, Edwin ten Winkel, bbPharma

Fluvoxamine (=Fluvox®), a selective serotonin reuptake inhibitor (SSRI) was tested for its ability to induce preputium eversion in Biomphalaria straminea in order to clarify the physiological mechanism of eversion. Biomphalaria straminea is a snail species that was accidentally introduced to Asia in recent years। Methioheptin and serotonin were added as controls. Fluvoxamine was found to have an MED of 10-50μM (p<0.0001). The receptor antagonist methiothepin was found to have an MED of 1 -10 μM (p <0.0001). Serotonin did not induce eversion and did not block methiothepin-induced eversion. This suggests that fluvoxamine is not acting as SSRI, but possibly as a receptor ligand.

Reference
Yapp, J.: Distribution of the Schistosome Vector Snail Biompholaria straminea: J. Mollus. Stud. 1990; 56: 47-55

Male preputium eversion in Biomphalaria alexandrina caused by SSRI's

Lam Hoi-ka, Edwin ten Winkel, bbPharma
Abstract. Eversion of the male preputium is an initial step in the copulatory behavior of several species of freshwater snails. Serotonergic mechanisms are involved in eversion in Biomphalaria glabrata snails as methiothepin, a serotonin receptor antagonist, has been shown to cause long-lasting dose-dependent eversion.
A number of selective serotonin reuptake inhibitors (SSRI's) were tested for their ability to induce preputium eversion in B. alexandrina in order to clarify the physiological mechanism of eversion. Methioheptin and serotonin were added as controls. Results were as follows: (SSRI's) fluoxetine (=Prozac®, 10–100 μM; p<0.0001), fluvoxamine (=Fluvox®, 10-50μM; p<0.0001), paroxetine (=Seroxat®, 10-50μM; p<0.0001). The receptor antagonist methiothepin (1 -10 μM; <0.0001). Serotonin did not induce eversion and did not block methiothepin-induced eversion. This suggests that the SSRI's are not acting as SSRI, but possibly as a receptor ligand.