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Electronic Journal of Pharmacology and Therapy Vol. 2, 35-38 (2009)
ISSN: 0973- 9890 (Available online at
Original Article
EFFECT OF TADALAFIL ON SEXUAL BEHAVIOR IN FEMALE RATS
ASWAR URMILA, M. AND BODHANKAR SUBHASH, L.
Department of Pharmacology, Bharati Vidyapeeth University, Erandawane, Paud Road, Received: April 15, 2009; Accepted: May 20, 2009 Abstract: The objective of the study was to evaluate and compare the effects of tadalafil and
sildenafil on sexual behavior in female rats. Female Wister rats (180 ± 10 g) showing estrous
phase were selected. The rats were divided into three groups (n=6). Group I was given vehicle,
group II was administered tadalafil (10 mg/kg p.o.) and group III was given sildenafil (10 mg/kg
p.o.). Drugs were administered to female rats one hour before copulatory behavior studies. They
were placed individually with male rat of proven fertility in a Plexiglass chamber. The female
sexual behavior was observed for 30 min. Our study indicated that tadalafil and sildenafil both
significantly decreased darting, hopping and lordosis latencies. Both increased darting hopping,
lordosis frequencies, anogenital grooming and licking behavior. Tadalafil was superior to
sildenafil in increasing lordosis duration. The results obtained in our study differentiated the
effects of tadalafil than sildenafil especially in consumatory phase of sexual behavior. Weak
effect of sildenafil in improving lordosis frequency and duration observed in present study may
be correlated with failure of sildenafil in clinical trials.
Key words: Female sexual dysfunction, Lordosis, Tadalafil
INTRODUCTION
that mediates smooth muscle relaxation and bloodengorgement [2]. The duration of action of cGMP is Female sexual dysfunction (FSD) is a new, rapidly controlled by phosphodiesterase (PDE) enzyme expanding area of sexual medicine. It is multicausal activity of which PDE5 is the major player in the and multidimensional disorder, which results in penis. The first PDE5 inhibitor for the treatment of significant personal distress, adversely impacting on male erectile disorder, sildenafil (Viagra), was life quality and interpersonal relationship. Current launched in 1998 and was followed by vardenafil epidemiological data reveal that up to 43 % of woman (Levitra) and tadalafil (Cialis). Following the enormous has some type of sexual dysfunction[1]. Approxima- success of PDE5 inhibitors in male, the attention was tely 10 million American women aged 50-74 years focused on female sexual dysfunction. In common complaints diminished vaginal lubrication, pain and with the penis, the clitoris is derived from the same discomfort with intercourse, decreased arousal and embr yonic stem cells and possesses corpus difficulty achieving orgasm. Lauamnn et al. [1] found cavernosal tissue. During female arousal, the vagina that sexual dysfunction is more prevalent in woman also becomes engorged. The presence of PDE5 in than in men and is associated with var ious woman’s clitoral and vaginal tissue [3,4], relaxation psychodemographic characteristics such as age, of human vaginal smooth muscle strips [5,6] and education and poor physical and emotional health.
increase blood flow into dog vagina and clitoris iswell reported in literature.
Male penile erection occurs following the release ofthe neurotransmitter nitric oxide, which results in Caruso et al. [7] has reported that sildenafil 25 and cyclic guanosine monophosphate (cGMP) production 50 mg/kg significantly improved sexual function i.e.
increased arousal, orgasm, enjoyment, satisfaction, to 55 % under 12:12-h light dark cycle. The animals frequency of intercourse and frequency of fantasies had free access to food pellets (Chakan Oil Mills, in premenopausal (22-28 yrs) woman. These Pune, India) and water was given ad libitum. The investigators noted that 70.5 % of women in the study experimenta l prot ocol wa s approved by the wanted to continue treatment with sildenafil. In Institutional Animal Ethics Committee (IAEC) of contrast to this, several large scale, placebo controlled Poona College of Pharmacy, Pune, constituted under studies including about 3000 women with female Committee for the Purpose of Control and Supervision sexual arousal disorder by the pharmaceutical company Pfizer, showed inconclusive results on theefficacy of sildenafil.
Treatment Schedule: Female Wister rats (180 ±
10 g) showing estrous phase were selected. The rats
Tadalafil, a Phophodiesterase 5 inhibitor, enables men were divided into three groups (n=6). Group I was with erectile dysfunction to achieve and maintain an given vehicle, group II was administered tadalafil (10 erection sufficient for successful intercourse with mg/kg p.o.) and group III was given sildenafil (10 sexual stimulation [8]. Its chemical structure differs mg/kg p.o.). Drugs were administered to female rats significantly from sildenafil [9]. Tadalafil (20 mg) one hour before copulatory behavior studies.
produces penile rigidity within 25-30 minutes. Theplasma half life of tadalafil amounts to be 17.5 hours Effect on sexual behavior : Experienced male
[10]. The effect of tadalafil on sexual behavior in Wister rats (200-250g) were used for the study. The normal female rats, however, has not been reported.
rectangular wooden box with plexiglass front and wire The objective of the study was to investigate the mesh top was used for the observations. One male effects of tadalafil and sildenafil on sexual behavior rat was then placed five minutes before introduction of female. The observations were made for 30minutes. The study was carried out at 2200-2400 MATERIALS AND METHODS
hrs under dim white light (30 lux). Sexual behavior infemale rats was studied by the methods described Chemicals: Sildenafil (Verma Pharmaceuticals,
by Giuliano et al. [11]. Sexual behavior was divided Pune) was obtained as gift sample, and tadalafil into prospective and receptive components.
(Macleodes Pharmaceutical Ltd.,Mumbai), waspurchased from market.
Proceptive behavior parameters: Dart ing,
hopping and orientational activities were observed
Animals: Female Wistar rats of weight range 180 ±
carefully. Dating is a short run where female abruptly 10 g and male Wistar rats (200-250g) were purchased stops presenting her posterior to male. Hopping is a from National Toxicology Centre, Pune, India and short jump with stiff legs followed by immobility and used for the study. They were maintained at a presentation and orientational activities are anogenital temperature of 25 ± 1 °C and relative humidity of 45 grooming, genital grooming and licking behavior.
Table 1: Effect of tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg p.o.) on darting, hopping and lordosis latencies. Figure in
parenthesis represents dose. Data represented are mean ± S.E.M (n=6) analysed by one way ANOVA followed by post hoc
Dunnets t test. #p<0.0001
Table 2: Effect of tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg p.o.) on darting, hopping and lordosis frequencies. Figure in
parenthesis represents dose. Data represented are mean ± S.E.M (n=6) analysed by one way ANOVA followed by post hoc
Dunnets t test. #p<0.0001
Table 3: Effect of tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg p.o.) on lordosis interval, anogenital grooming, genital grooming
and licking behavior in female rats. Data represented are mean ± S.E.M in female rats (n=6) analysed by one way ANOVA followed
by post hoc Dunnets t test. #p<0.0001, **p<0.001.
Receptive behavior parameters: Lordosis -
showed 4.17 ± 0.60 hops and sildenafil (10 mg/kg behavior posture assumed by female to allow p.o.) treated animals showed 5.83 ± 0.95 hops.
mounting by male was also carefully examined.
Treatment with sildenafil and tadalafil increasednumber of hops significantly (p<0.0001). (Table 2).
Statistical analysis: Data for each of the parameter
was analyzed by one-way ANOVA followed by
Lordosis latency: The time taken to achieve lordosis
Dunnets post hoc test using Graph Pad, Prism by female rats in control group was 1170 ± 96.436 seconds where as in tadalafil (10 mg/kg p.o.) groupit was 340 ± 42.89 seconds. In sildenafil (10 mg/kg p.o.) treated rats the lordosis latency was 488.83 ±73.08 seconds. The lordosis latency was significantly Darting latency: The time taken to initiate the short
reduced in sildenafil and tadalafil treated group run made by female rats in front of male exposing their posterior was considered as darting. The dartinglatency observed in control group was 628.33 ± Lordosis frequency and duration: The lordosis
132.97 seconds, while that of tadalafil (10 mg/kg p.o) frequencies in female rats were control 1.0 ± 0.0, and sildenafil group it was 83.33 ± 14.29.seconds tadalafil (10 mg/kg p.o.) treated group it was 3.0 ± and 218.33 ± 36.37 seconds respectively. The tadalafil 0.26 while in sildenafil group (10 mg/kg p.o.) it was and sildenafil group showed significantly (p<0.0001) 1.66 ± 0.33. The lordosis frequency was significantly less latency period as compared to control group.
(p<0.0001) high in sildenafil and tadalafil treated Tadalafil was more effective in reducing darting group. The duration of lordosis was significantly latency compared to sildenafil group. (Table 1).
(p<0.001) more in tadalafil treated group thansildenafil group. (Table 3).
Darting frequency: The number of darting recorded
for 30 minutes period 1 hour after administration of
Anogenital grooming: Sildenafil (10 mg/kg p.o.)
drugs in control group was 6.5+1.23 while that of and tadalafil (10 mg/kg p.o.) significantly increased tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg p.o.) anogenital grooming (p<0.001) compared to control group was 15.33+0.76, 8.33+1.23 respectively. The darting frequency was significantly higher in tadalafilgroup and sildenafil group (p<0.0001) than control Genital grooming: No significant increase was
observed in sildenafil (10 mg/kg p.o.) and tadalafil(10 mg/kg p.o.) group as compared to control group.
Hopping latency: Hopping is characterized by a
short jump with stiff legs followed by immobility anda presenting behavior. Hoping latency seen in control Licking: Sildenafil (10 mg/kg p.o.) and tadalafil (10
rats was observed to be 900 ± 120.99 seconds while mg/kg p.o.) significantly increased licking behavior in tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg (p<0.001) compared to control group. (Table 3).
p.o.) group it was found to be 350.0 ± 44.94, 298.0 ±54.92 seconds respectively. The hopping latencies DISCUSSION
were significantly decreased by both tadalafil andsildenafil (p<0.0001). (Table 1).
Gonadally intact female rats of reproductive age gointo sexual heat every hour to five days immediately Hopping frequency: Control group exhibited 1.83
after ovulation. This process is imitated by the ± 0.30 hops, tadalafil (10 mg/kg p.o.) treated group sequential actions of the estrogen and progesterone in brain and periphery, so that sexual behavior shows behavior parameters like genital stimulation, an “estrous cycle” [12]. Peripheral sexual reflexes, masturbation, copulation and orgasm in human female copulatory behavior, and appetitive conditioned sexual [12]. The results obtained in our study differentiated responses have been examined in female rats, rabbits, the effects of tadalafil than sildenafil especially in and primates such as macaques. The physiologic consumatory phase of sexual behavior. Weak effect mechanisms that regulate vaginal blood flow are of sildenafil in improving lordosis frequency and extremely similar between species, and more is duration observed in present study may be correlated known about the hormonal and neural regulation of with failure of sildenafil in clinical trials.
the reflexive posture lordosis than any other sexualreflex [13].
It is concluded that tadalafil improved consumatorybehavior especially higher lordosis frequency and Female sexual behavior can be divided into sequential duration compared to sildenafil. The beneficial effects precopulatory and consumatory components. In the of tadalafil on female sexual disorder needs to be female rats these aspects of sexual behavior are also referred to as proceptive and receptive component,two different aspects of sexual behavior are displayed REFERENCES
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