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EXPLORATORY EVALUATION OF NOVEL, NON-HORMONAL MALE CONTRACEPTIVE
DRUG PROTOTYPES ACTING IN VAS DEFERENS
Nnaemeka I.B. Amobiab
and I. Christopher H. Smith; King's Collegea, London SE1 1UL.
Joanna Cocker, Melanie Wood and Ruth Turl; Royal Veterinary College, Hatfield Campus, AL9 7TA
John Guillebaud; Elliot-Smith Clinic b, Churchill Hospital, Headington, Oxford, OX3 7L J
1 BACKGROUND The development i s based on our discovery of the mode of drug action for a
side-effect shared by two therapeutic drugs, thioridazine and phenoxybe
nzamine (PBZ)
INHIBITION OF SEMEN EMISSION, WHICH OCCURS WITHOUT AFFECTING PENILE ERECTION, ORGASM
OR LIBIDO
1.Greenberg H R & Carrillo C (1968). Thioridazine-induced inhibition of masturbatory ejaculation in an adolescent. The American journal of 2.Singh H (1963). Therapeutic use of thioridazine in premature ejaculation. The American journal of psychiatry, 119, 891.
3.Kedia K R & Persky L (1981). Effect of phenoxybenzamine (dibenzyline) on sexual function in man. Urology, 18(6), 620-1.
4.Homonnai Z T, Shilon M & Paz G F (1984). Phenoxybenzamine--an effective male contraceptive pill. Contraception, 29(5), 479-91.
The potential
of PBZ as a male contraceptive was tested by Homonnai et al.(1984) – Reported total inhibition of semen emission
within 3-4 days with little probability of female impregnation thereafter. Ejaculate recovery occurred within 5 days after cessation of
dosing. However, for medical reasons PBZ and thioridazine are unsuitable for routin
e male contraceptive purposes.
PROPULSIVE MECHANISM AND MODE OF DRUG ACTION UNDERLYING THE SIDE EFFECT
Dual effect of longitudinal muscle
inactivation (persistent tissue slack) and
unabated circular muscle contractility
(lumen closure) disrupts the coordinated
activity that sustains efficient propulsive
function in semen emission.
CURRENT STUDY - NOVEL PROTOTYPES
[diphenyl- aryloxy- alkylamine deriv atives]
replicating this action in human and ram
vasa were evaluated in vivo
in order to
identify prototypes producing ≥ 50%
reduction in ram ejaculate within 4-16 hr.
PROTOTYPE XN73 – DIFFERENT DOSES
REDUCED IN VIVO EJACULATE SPERM CONTENT & VOLUME IN TWO RAMS BY 67- 83%
3 RESULTS
BLOOD SAMPLE ANALYSIS - XN73 plasma levels
were 16.7 ng/ml (IV - 0.67 mg/kg) and 66.2 ng/ml (IV - 1.4 mg/kg) after 4 hr of administration but declined rapidly to undetectable levels (animal 1) & 10 ng/ml (animal 2) within 16 hr. IN SILICO ANALYSIS of microspecies revealed a
predominance of ionized microspecies with zero un-
ionized microspecies at pH 1.5, 5.0, 6.5 & 7.4. The
decline in plasma drug levels and inadequate
microspecies distribution underlie the less than
100% efficacy in the ram experiments and corrected [TM; time-matched controls (saline), Interval between tests with saline (controls) and drug prototypes – 12 days] for in the latest chemically modified prototypes.
PROTOTYPE XN6 – REDUCED IN VIVO
SPERM CONTENT & VOLUME BY 64 – 66%
CONCLUSION
The prototypes, though unoptimized, have
BLOOD SAMPLE ANALYSIS
demonstrable potential in terms of
¾ Short-term inhibition of semen
emission for male contraception &
(1.4 mg/kg IV) after 4 hr and within 16 hr were 94 ng/ml (animal 3; IV ¾ Drug-like properties
1.34 mg/kg) and 0-0.6 ng/ml Collaborative milestone-based funding is required to
(animal 4; IV 0.7 & 1.4 mg/kg) .
start work on evaluating the modified prototypes
select drugs with the best contraceptive efficacy
We gratefully acknowledge the
support of CONRAD (USA) for this
profile, oral bioavailability, metabolic stability and
pivotal in-vivo prototype study.
safety attributes.

Source: http://www.parsemusfoundation.org/wp-content/uploads/2012/11/FOCI_Poster_Revised26Oct_Amobi_et_al.pdf

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Synonyms: Salt; Rock Salt; Saline; Table Salt CAS No.: 7647-14-5 Molecular Weight: 58.44 Chemical Formula: NaCl Manufacturer/Supplier: Globe Chemicals GmbH Spohrstr. 2 D-22083 Hamburg Deutschland 2. Composition/Information on Ingredients Ingredient CAS No Percent Hazardous --------------------------------------- ------------ ------------ --------- Sodium Chloride 7647-14-5 99 -

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