D-Cloprostenol

D-Cloprostenol

Brand: Full Catalog
Product Code: DC30
Availability:
In Stock
Price: $62.00
Description

D-CLOPROSTENOL: PGF2a Super-Agonist - 50mcg / ml, 60ml

D-cloprostenol, also called (+)-cloprostenol sodium, is a highly potent prostaglandin F2-alpha analog with selective agonistic activity at the FP receptor.  It binds to the prostaglandin FP receptor with two-hundred-fold greater affinity than physiological prostaglandin F2 alpha (PGF2a), one-hundred-fold greater affinity than bimatoprost, and fifty-fold greater affinity than latanoprost.   The prostaglandin compound family have recently become a topic of increased interest due to a study by Cotsarelis and Garza [1], which found that prostaglandin D2 (PGD2) likely plays a key role in inducing male androgenic alopecia (AA), also known as male pattern baldness.  Though chemically related, effects of compounds within the prostaglandin family can vary greatly or be opposite in nature.  Research from within the last decade highlights hair-regrowth effects of PGF2a analogs [2,3] that may hold increased relevance for new drug development strategies for hair regrowth in light of the new information about PGD2’s baldness-inducing effects.

Colombe et al write that the weight of evidence “suggests that this local prostaglandin production might somehow be involved in hair growth control and differentiation” [2] and Wolf et al write that “PG activators (PGF2a analogs) might show even better results [than PGF2a itself]” and argue that from a drug development standpoint, should be “first drugs of choice for [male pattern baldness] [due to] achieving greater therapeutic success than other currently available preparations“ [3].

The primary mechanism behind the hair-growth induced by prostaglandin analogs such as cloprostenol is mediated by the FP receptor, but other mechanisms such as alteration in gene expression and changes in metabolism or production of other prostaglandins (such as reduction of prostaglandin D2) may also exist.

A major breakthrough in the link between prostaglandins and hair-growth occurred when the latanoprost and bimatoprost were discovered to induce eyelash growth in patients being treated for ocular hypertension:

“The prostaglandin F2α analogues latanoprost and bimatoprost are used in treating ocular hypertension and glaucoma. A noted side effect was increased eyelash hair growth, a feature that has been investigated in several small scale studies. Bimatoprost (Latisse®) is now available as a treatment for eyelash growth.21 More recently, latanoprost (Xalatan®) has been investigated for its potential to promote scalp hair growth. Latanoprost significantly increased hair density compared with baseline and placebo and may also encourage pigmentation.[4]”

The hair-growth effects have been observed for multiple analogs of PGF2a; in addition to the FP receptor Colombe et al suggest that it may affect upstream conversion of prostaglandin H which could influence metabolism at the follicle site:

“The PGE2 and PGF2α were also described as possible modulators of hair growth. Indeed, topical use of viprostol, a PGE2 analogue, was reported to increase human hair growth and terminal hair counts after 50 weeks treatment (11) while administration of 16,16-dimethyl PGE2 protected mice from radiation-induced alopecia (12). Minoxidil, a potent trichogenic agent, was found to enhance prostaglandin endoperoxide synthase-1 (PGHS-1) activity, suggesting a link between prostaglandin synthesis and hair growth (13), as later confirmed by the role of PGHS-2 in the control of hair cycle (14). Latanoprost, a PGF2α analogue used to treat glaucoma, was reported to induce hypertrichosis in humans (15) and stump-tailed macaque (16). Moreover, as isopropyl unoprostone and PGF2α, it stimulated conversion from the telogen to the anagen phase in mice model (17). On the contrary, cyclooxygenases (COX)-2 overexpression induced a reduction in hair follicle density and delayed postnatal hair follicle morphogenesis in transgenic mice compared with wild-type animals while COX-2 inhibitors restored normal hair growth (18,19).[2]”

Perhaps the most promising research yet was done on an animal model of baldness, the stump-tailed macaque; the results demonstrate that PGF2a analogs may be relevant for treatment of androgenic alopecia in primates, and, according to the researchers, humans:

“Eight monkeys were divided into 2 groups; one group received a daily topical application of 50 microg/ml of latanoprost for 5 months; a control group had a daily application of vehicle. For an additional 3 months, 2 monkeys from each group were given 500 microg/ml latanoprost, while the remaining monkeys continued with the previous treatment. Hair growth was evaluated by monthly photographs and phototricho-graphic analysis. Fifty microg/ml of latanoprost caused minimal hair growth. Latanoprost at 500 microg/ml induced moderate to marked hair regrowth with 5-10% conversion of vellus hairs to intermediary or terminal hairs. The vehicle group showed no effect. Further evaluation of latanoprost as an agent for treatment of human androgenetic alopecia is indicated.[5]”

One potential issue of using latanoprost or other relatively weak PGF2a agonists is that since the lower dose-range (50mcg/ml, which is comparable to the dose found in commercial products Latisse and Lumigan) was found ineffective when applied to the scalp, a higher dose of a weak PGF2a analog such as latanoprost could be cost-prohibitive.

As a much more powerful analog of PGF2a with selective superagonist activity at the FP receptor, cloprostenol may be a more promising compound for further drug development taking into account cost of production.  With an effective concentration (EC50) of 0.84 nM and full agonist activity[6] at the FP receptor, cloprostenol is many times more potent than PGF2a, latanoprost, or bimatoprost.  In the same study Griffin et al find that PGE2 is ineffective at the FP receptor[6].

At approximately fifty times greater potency than latanoprost, d-cloprostenol may be a much more cost-effective choice for eventual drug development if high concentrations are required for hair regrowth.

In humans, a dose of 100 mcg/ml latanoprost was found to be moderately effective in inducing regrowth:

“Latanoprost significantly increased hair density (terminal and vellus hairs) at 24 weeks compared with baseline and the placebo-treated area. Latanoprost could be useful in stimulating hair follicle activity and treating hair loss.” [7]

Johnstone et al describe the clinical observation of hair growth induced by latanoprost and offer comment on the efficacy of even brief therapy (2-17 days):

“Latanoprost, used clinically in the treatment of glaucoma, induces growth of lashes and ancillary hairs around the eyelids. Manifestations include greater thickness and length of lashes, additional lash rows, conversion of vellus to terminal hairs in canthal areas as well as in regions adjacent to lash rows. In conjunction with increased growth, increased pigmentation occurs. Vellus hairs of the lower eyelids also undergo increased growth and pigmentation. Brief latanoprost therapy for 2-17 days (3-25.5 microg total dosage) induced findings comparable to chronic therapy in five patients. Latanoprost reversed alopecia of the eyelashes in one patient. Laboratory experiments with latanoprost have demonstrated stimulation of hair growth in mice and in the balding scalp of the stumptailed macaque, a primate that demonstrates androgenetic alopecia. The increased number of visible lashes is consistent with the ability of latanoprost to induce anagen (the growth phase) in telogen (resting) follicles while inducing hypertrophic changes in the involved follicles. The increased length of lashes is consistent with the ability of latanoprost to prolong the anagen phase of the hair cycle. Correlation with laboratory studies suggests that initiation and completion of latanoprost hair growth effects occur very early in anagen and the likely target is the dermal papilla.[8]”

Research by Stjernschantz “found a significant hypertrichotic effect of a selective prostanoid receptor agonist (fluprostenol) on hair growth as determined by measuring the rate of the regrowth of fur in adult male CBA-J mice” [3] demonstrating that the effect of PGF2a on hair follicles is persistent across different PGF2a analogs as well as different species.

A separate study of a mouse model found several different types of pro-hair-growth stimulatory effects  were induced by three different FP receptor agonists, an effect increased by the presence of PGE2:

Latanoprost and isopropyl unoprostone, which are analogues of prostaglandin F2alpha (PGF2alpha), are promising drugs for the reduction of intra-ocular pressure. However, they have been reported to have side effects, including hypertrichosis and hyperpigmentation of the eyelashes and periocular skin…. In order to investigate these effects further, PGF2alpha, latanoprost and isopropyl unoprostone were applied to the dorsal skin of 7-week-old C57BL/6 mice, and hair length was measured during the treatment. The three molecules all showed stimulatory effects on the murine hair follicles and the follicular melanocytes in both the telogen and anagen stages, and stimulated conversion from the telogen to the anagen phase. PGE2 is known to act synergistically with PGF2alpha, and hence the influence of PGE2 was also examined. PGE2 did not induce distinct telogen-to-anagen conversion, but showed moderate growth stimulatory effects on early anagen hair follicles. In addition, we observed a case of hypertrichosis and trichomegaly. The stimulatory effects of PGF2alpha and PGE2 on hair growth have been discussed with regard to the role of protein kinase C and mast cells.[9]

Exogenous PGF2a and analogs reverse indomethacin-induced inhibition of endogenous PGF2a production.[10]

 

Resources

[1] Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, Loy DE, Zhao T, Blatt HB, Stanton DC, Carrasco L, Ahluwalia G, Fischer SM, FitzGerald GA, Cotsarelis G. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012 Mar 21;4(126):126ra34.

[2] Colombe L et al. Prostaglandin metabolism in human hair follicle. Exp Derm. Vol 16, 9, p762–9, Sept 2007.

[3]Wolf R, Matz H, Zalish M, Pollack A, Orion E. Prostaglandin analogs for hair growth: Great expectations. Dermatology Online Journal 9(3): 7

[4] Kevin J. McElwee, PhD and Jerry Shapiro, MD, FRCPC. Promising Therapies for Treating and/or Preventing Androgenic Alopecia. Skin ther. Let.

[5]Uno H, Zimbric ML, Albert DM, Stjernschantz J. Effect of latanoprost on hair growth in the bald scalp of the stump-tailed macacque: a pilot study. Acta Derm Venereol. 2002;82(1):7-12.

[6] Griffin BW, Magnino PE, Pang IH, Sharif NA. Pharmacological characterization of an FP prostaglandin receptor on rat vascular smooth muscle cells (A7r5) coupled to phosphoinositide turnover and intracellular calcium mobilization. J Pharmacol Exp Ther. 1998 Jul;286(1):411-8.

[7] Blume-Peytavi U, Lönnfors S, Hillmann K, Garcia Bartels N. A randomized double-blind placebo-controlled pilot study to assess the efficacy of a 24-week topical treatment by latanoprost 0.1% on hair growth and pigmentation in healthy volunteers with androgenetic alopecia. J Am Acad Dermatol. 2012 May;66(5):794-800. doi: 10.1016/j.jaad.2011.05.026. Epub 2011 Aug 27.

[8] Johnstone MA, Albert DM. Prostaglandin-induced hair growth. Surv Ophthalmol. 2002 Aug;47 Suppl 1:S185-202.

[9] Sasaki S, Hozumi Y, Kondo S. Influence of prostaglandin F2alpha and its analogues on hair regrowth and follicular melanogenesis in a murine model. Exp Dermatol. 2005 May;14(5):323-8.

 [10] Walch et al. Prostaglandin (PG) FP and EP1 Receptors Mediate PGF2α and PGE2 Regulation of Interleukin-1β Expression in Leydig Cell Progenitors Endocrinology 144 (4): 1284. 4/2003.

Reviews (0)

Write a review



Note: HTML is not translated!

Bad            Good

Related Products