The effect of Amantadine on Clomipramine induced sexual dysfunction in male rats.
The sexual act involves central as well as peripheral mechanisms. (1) Several mediators are involved in the central mechanisms. It is well established that noradrenaline, (2,3) serotonin,4,5 and dopamine are involved in the central mechanisms. (4,5) Noradrenaline plays an excitatory role, while the role of serotonin is inhibitory.
Clomipramine (Clmp) is a tricyclic antidepressant, which has demonstrated efficacy in depression, obsessive compulsive disorder (OCD) and panic disorder. Clomipramine is the imipramine analogue of chlorpromazine. Due to its action against anxiety disorders and panic attacks, it is the only drug with 2 entries in the essential drugs list of the World Health Organization (WHO). With regards to compulsive disorders, it is now the "gold standard" of therapy against which other drugs are measured. (6-10) However, chronic use of Clomipramine leads to sexual dysfunction in humans (11,12) and neonatal males. (13)
Compared to other tricyclic antidepressants, Clomipramine has much greater effect on dopamine blockade and serotonin reuptake inhibition. (14) These implicate the prolactin release and orgasmic dysfunction mediated through 5-[HT.sub.2] receptors. (15,16) Moreover, peripheral antimuscarinic, (17) and alpha adrenergic blockade effects have been implicated in the Clomipramine induced sexual dysfunction.11,12,18 There are few studies of clinical management of Clomipramine induced sexual dysfunction. Case reports and open trials have suggested that Yohimbine, (19) Bupropion, (20) Cyproheptadine, (21) and Amantadine, (22,23) may be effective in the antidepressant induced sexual dysfunction.
Hence, the present study was conducted to find out whether dopamine agonists such as Amantadine can antagonize the Clomipramine induced sexual dysfunction in male rats. Amantadine acts by increasing dopamine levels centrally, increasing dopamine release, inhibiting amine uptake, or through direct action on dopamine receptors.24 The doses were selected by extrapolating the human therapeutic dose to rats based on the body surface area. (25)
The Clomipramine doses selected were 1/2TD, TD, 2TD considering 300 mg as the maximum human therapeutic dose per day and it was found to be 13.5 mg/kg, 27 mg/kg and 54 mg/kg respectively. The influence of Amantadine on Clomipramine induced sexual dysfunction was tested with Amantadine (9 mg/kg) considering 100 mg as the maximum human therapeutic dose.
A total of 48 male and 48 female Sprague-Dawley albino rats were purchased from central animal house NIMHANS, Bangalore. All animals were housed in a group of six males and females separately in plexi glass cages (62 x 40 x 21) in an acclimatized colony room (25 [+ or -] 0.5[degrees]C) maintained on a 12/12 hr light/dark cycle. The rats were 4 months old. The males weighed around 300-400 gm each and females weighed 250-350 gm each. They were fed on commercial pellet feed and water was available ad libitum. The study was approved by the Institutional Ethical Committee prior to commencement.
The male rats were randomly divided into four groups of 12 male rats each. Group I served as controls. Group II, III, and IV were treated with Amantadine (9 mg/kg body weight, p.o) 30 min, prior to the treatment with 13.5 mg/kg, 27 mg/Kg and 54 mg/ Kg bodyweight p.o of Clomipramine respectively for 60 days. The control group received vehicle 1 ml / kg p.o. All the animal studies were carried out after 7 PM in the animal house of Sri K.V College of Pharmacy, Chickballapur.
The sexual behavior of the male rats was studied as explained elsewhere, (26) the copulatory behavior of the male rat was characterized by a series of mounts with or without vaginal intromission from the rear of the female approximately once in every 30 to 120 sec, that eventually culminates in ejaculation. The females responded to each mount with a lordosis response, namely; a dorsoflexion of the spine and deflexion of the tail to one side allowing vaginal access for the male.
Typically, the male achieves vaginal penetration on 5080% of the mounts. Intromission patterns can be distinguished behaviorally from mounts with penetration by the presence of deep thrust and springing dismount. (27) A mount was defined as the male's pelvis intentionally coming into contact with the female's haunch with accompanying hip movements from the male. An intromission was identified when the male mounted and achieved insertion of the penis into the female as marked by deeper than normal thrust usually followed by abrupt movement away from the female, urgent front leg movements and grooming. Ejaculation was marked by a more profound thrust than that of regular intromission and was followed not by movement away from the female, but by sudden limpness and immobility until the female moves away. After ejaculation and immobility, the male was engaged in the long period of grooming (5-10 min) post ejaculation pause. (26)
An ejaculation occurred after 6-15 intromissions and was followed by a period of 5-10 minutes post ejaculatory interval during which the male is refractory to further copulatory activity. The number of intromissions and latency to ejaculate at first decreases and then subsequently increases with increasing number of ejaculations. (27) The ejaculatory activity of males was confirmed by observing the vaginal smear of the females for the presence of male sex cells. The following parameters were recorded: mount latency (Time taken for the first mount from the introduction of the female into the male cage), intromission latency (Time taken for the first intromission from the introduction of females into the males' cage), ejaculation latency (intervals between the first intromission to the first ejaculation), post ejaculatory pause (Time interval between ejaculations to the next mount/intromission), intromission frequency (Number of intromissions preceding ejaculation) and Mounting frequency (Number of mounts preceding ejaculation).
Using these measures the following parameters were computed: % mounted, % intromitted, % ejaculated, copulatory efficiency (Number intromissions/number of mounts + number intromission) and inter copulatory interval (Average time interval between intromissions).
Half of the animals in each group were sacrificed on 30th day and the remaining on 60th day for blood sample collection and for histopathological examination of the testes. Blood was collected through the cardiac puncture using a 16 no. needle under mild ether anesthesia and allowed to stand for 20 minutes. After centrifugation, serum was separated and stored at -20[degrees]C for subsequent hormonal estimation. The testes were also collected and processed in Bouin's fluid, (28) for the histopathological studies. The sections were examined under high power microscope. The evaluation of the cell population was based on the calculation made for each type of developing sperm cells per cross section of ten randomly selected seminiferous tubules. The sertoli cells, spermatogonia, secondary spermatocytes and spermatids were counted under 100x magnification. (29,30)
In terms of the Amantadine and Clomipramine combined influence on sexual behavior of male rats, the number of rats intromitted and ejaculated was reduced, dose dependently and time dependently in the 1/2TD and TD Clomipramine treated groups. However, in 2TD group, suppression of libido was observed on 60th day. The number of rats intromitting and ejaculating was further reduced when compared to 1/2TD and TD group. Hence Amantadine failed to antagonize the effect of Clomipramine on sexual behavior. All the latencies for example mount latency, intromission latency and ejaculation latency were increased significantly compared to the controls. The results also conveyed a decrease in the number of intromissions and an increase in the number of mounts, thus leading to a decrease in the copulatory efficiency. Post ejaculation pause was also increased when compared to controls. (Table 1)
With regards to the combined effect of Amantadine and clomipramine on serum testosterone level; the results showed a significant dose dependent decrease in the mean serum testosterone levels in the TD Group and 2TD Group after 30 days treatment. At the end of the 60 days, the mean testosterone levels were further reduced in the TD Group and 2TD Group animals. (Table 2)
The combined effect of both Amantadine and clomipramine on the histology of the testes at the end of 30 days revealed no significant changes between the control group and 1/2TD group. Hence, a significant reduction in spermatogonia, spermatids and secondary spermatocytes was observed in the TD group. While in the 2TD group, a reduction in Sertoli cells, spermatogonia, spermatids and secondary spermatocytes was observed. Hence Amantadine had not offered the animals any protection at higher doses of Clomipramine. After 60 days of treatment, the decrease in sperm cell count was also continued with higher doses of Amantadine + Clomipramine. Thus no significant changes were observed between 1/2TD group and the Clomipramine treated control group. Therefore, Amantadine could not be a safe antidote for the treatment of Clomipramine induced sexual dysfunction. (Table 3, Figs. 1A-G)
[FIGURE 1 OMITTED]
In this study, the hormonal and peripheral testicular parameters indicate that Amantadine, a dopamine agonist did not change the Clomipramine induced sexual dysfunction in male rats. Pharmacological evidence demonstrated that the elevation of cerebral levels of 5-HT affects the secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), for inhibiting the liberation of gonadotrophin releasing hormone (GnRH) in the hypothalamus, with subsequent effects on the process of spermatogenesis and steroidogenesis in adult rats. (31,32) Serotonin is present in the testis and accessories glands, besides many organic tissues. In these glands, monoaminoxidase, the enzyme that metabolizes 5-HT is also detected. (33-36) In rats, the testicular 5-HT can originate from the nerve endings in the capsule, the mast cells and the Leydig cells. (34,35,37) In the testis, the 5-HT can reduce the steroidogenesis and spermatogenesis by decreasing the intra-testicular flow due to arterial constriction or by inhibiting the fundamental enzymes for steroidogenesis. (38,39) On the other hand, a number of reports indicate that dopamine is involved in sexual function. (40,41)
Earlier reports have also indicated that Clomipramine causes a decline in testicular cell development in male rats treated with 1/2TD, TD and 2TD of clomipramine. (42) Hence Amantadine, a dopamine agonist was used to determine its usefulness on the ability to antagonize the Clomipramine induced sexual dysfunction. The study revealed that Amantadine did not antagonize Clomipramine induced sexual dysfunction and hence is not useful to treat Clomipramine induced sexual damage in male rats. As per the reports, (43-45) Amantadine did not possess dopamine agonistic action in rats. The same reason may be responsible for the absence of efficacy against Clomipramine induced sexual dysfunction.
In the sexual behavior study, the number of rats mounted, intromitted and ejaculated was decreased, dose dependently and time dependently. Prolongation of intromission latency, ejaculation latency and post ejaculation pause were also continued with Amantadine treatment. Copulatory efficiency also decreased gradually, dose dependently and time dependently indicating that erection failure was continued. Overall, Amantadine failed to improve sexual behavior of male rats treated with different doses of clomipramine in the sexual behavior study. The Amantadine + Clomipramine 27 mg/kg reduced the level of serum testosterone, dose dependently and time dependently. This indicates that Amantadine also failed to alter the Clomipramine induced decline in testosterone levels. (Table 2)
All the parameters measuring spermatogonia, spermatids and secondary spermatocytes were significantly decreased dose dependently, mostly due to decreased levels of FSH, LH and testosterone, which are essential for the completion of the spermatogenesis process. Overall, it appears that Amantadine did not offer any protection against Clomipramine induced sexual dysfunction. The testes are the gonads in males and contain three different types of cells namely: Leydig cells (responsible for the production of testosterone); spermatogonia (responsible for spermatogenesis, i.e., sperm cells) and Sertoli cells (responsible for the secretion of androgen binding protein, inhibin, sulfated glycoprotein-2 and transferrin). (46) FSH is responsible for the development and differentiation of spermatogonia through different stages namely spermatogonia, preleptotene, leptotene, early pachytene, late pachytene, and secondary spermatocytes after the attainment of puberty. (47) FSH acts predominantly to support spermatogonial (SG) number, to prevent the premature degeneration of SGs and spermatocytes (SCs). The principal effect of testosterone is to facilitate the progression of SCs in further stages of spermatogenesis, perhaps by maintaining their attachment to Sertoli cells. (46) In other words, FSH is responsible for sperm maturation, while LH is responsible for steroidogenesis. (48)
Brown and Redfern in1976 reported that the anti-parkinsonian effect of Amantadine was not mediated through dopamine. Furthermore, Mercur et al. (1991) concluded that Amantadine failed to elevate the dopamine levels in the rat substantia nigra, zona compacta neurons. While Kornhuber and Weller (1993) confirmed that the anti-parkinsonian effect of Amantadine was due to its action against N-methyl-D-aspartate (NMDA) type of glutamate receptor. Hence the above findings indicate that anti-parkinsonian effect of Amantadine may not be mediated with elevation of dopamine, as our results also substantiate the above findings. The results also indicated that Amantadine did not influence dopamine mechanism and it was not effective in improving the condition of Clomipramine induced sexual dysfunction in rats.
The present study revealed that Amantadine, a dopamine agonist failed to antagonize the Clomipramine induced sexual dysfunction in male rats. The fall in testosterone, sexual behavior and sperm cell count were continued even in the presence of Amantadine. The results also indicate that Amantadine unable to antagonize the VTD Clomipramine induced sexual dysfunction in male rats. Moreover, Amantadine could not be considered a safe antidote to treat Clomipramine induced sexual dysfunction in male rats.
The authors reported no conflict of interest and no funding was received for this work.
Received: 24 Jun 2011/ Accepted: 16 Sept 2011
(1.) Stief CG. Central mechanisms of erectile dysfunction: what a clinician may want to know. Int J Impot Res 2003 Apr;15(Suppl 2):S3-S6.
(2.) Bancroft J, Munoz M, Beard M, Shapiro C. The effects of a new alpha-2 adrenoceptor antagonist on sleep and nocturnal penile tumescence in normal male volunteers and men with erectile dysfunction. Psychosom Med 1995 Jul-Aug;57(4):345-356.
(3.) Guiliano F, Rampin O. Central adrenergic control of penile erection. Int J Impot Res 2000;12(suppl):S13-S19.
(4.) Hull EM, Muschamp JW, Sato S. Dopamine and serotonin: influences on male sexual behavior. Physiol Behav 2004 Nov;83(2):291-307.
(5.) Zvi Zemishlany & Abraham Weizman. The impact of mental illness on sexual dysfunction. Adv Psychosom Med. Basel, Karger, 2008, vol 29, pp 89-106
(6.) Rothschild AJ. New directions in the treatment of antidepressant-induced sexual dysfunction. Clin Ther 2000;22(Suppl A):A42-A57, discussion A58-A61.
(7.) Baldwin DS. Psychotropic drugs and sexual dysfunction. In. Rev. Psychiatry. 1995;7:262-273.
(8.) Lane RM. A critical review of selective serotonin reuptake inhibitor-related sexual dysfunction; incidence, possible aetiology and implications for management. J Psychopharmacol 1997;11(1):72-82.
(9.) Fava M, Rankin M. Sexual functioning and SSRIs. J Clin Psychiatry 2002;63(Suppl 5):13-16, discussion 23-25.
(10.) Bernick M, Antonio HG, Nunea PV. Bethanechol chloride for treatment of clomipramine induced orgasmic dysfunction in males. Rev. Hosp. Clinic. Fac. Med. Paulo S. 2004;59(6):357-360.
(11.) Balon R, Yeragani VK, Pohl R, Ramesh C. Sexual dysfunction during antidepressant treatment. J Clin Psychiatry 1993 Jun;54(6):209-212.
(12.) Beaumont G, Mayes A. Do task and sex differences influence the visual evoked potential? Psychophysiology 1977 Nov;14(6):545-550.
(13.) Feng P, Guan Z, Yang X, Fang J. Impairments of ERK signal transduction in the brain in a rat model of depression induced by neonatal exposure of clomipramine. Brain Res 2003 Nov;991(1-2):195-205.
(14.) Blackwell B. Antidepressant drugs. In: Dukes MN Meyer's side effects of drugs. Elsevier, Amsterdam. 1984; 24-61.
(15.) Jones RB, Luscombe DK, Groom GV. Plasma prolactin concentrations in normal subjects and depressive patients following oral clomipramine. Postgrad Med J 1977;53(Suppl 4):166-171.
(16.) Pomerantz SM, Hepner BC, Wertz JM. Serotonergic influences on male sexual behavior of rhesus monkeys: effects of serotonin agonists. Psychopharmacology (Berl) 1993;111(1):47-54.
(17.) Sorscher SM, Dilsaver SC. Antidepressant-induced sexual dysfunction in men: due to cholinergic blockade? J Clin Psychopharmacol 1986 Feb;6(1):53 55.
(18.) Aizenberg D, Zemishlany Z, Hermesh H, Karp L, Weizman A. Painful ejaculation associated with antidepressants in four patients. J Clin Psychiatry 1991 Nov;52(11):461-463.
(19.) Price J, Grunhaus LJ. Treatment of clomipramine-induced anorgasmia with yohimbine: a case report. J Clin Psychiatry 1990 Jan;51(1):32-33.
(20.) Walker PW, Cole JO, Gardner EA, Hughes AR, Johnston JA, Batey SR, et al. Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion. J Clin Psychiatry 1993 Dec;54(12):459-465.
(21.) Aizenberg D, Zemishlany Z, Weizman A. Cyproheptadine treatment of sexual dysfunction induced by serotonin reuptake inhibitors. Clin Neuropharmacol 1995 Aug;18(4):320-324.
(22.) Balogh S, Hendricks SE, Kang J. Treatment of fluoxetine-induced anorgasmia with amantadine. J Clin Psychiatry 1992 Jun;53(6):212-213.
(23.) Balon R. Intermittent amantadine for fluoxetine-induced anorgasmia. J Sex Marital Ther 1996;22(4):290-292.
(24.) Rang HP, Dale MM, Ritter JM, Flower RJ. Pharmacology, 6th Ed, Churchill Livingstone. 2007; pp 520.
(25.) Silva JV, Lins AM, Amorim JA, Pinto CF, Deiro TB, Oliveira JR, et al. Neonatal administration of fluoxetine decreased final sertoli cell number in Wistar rats. Int. J. Morphol. 2008;26(1):51-62.
(26.) Dissanayake DM, Wijesinghe PS, Ratnasooriya WD, Wimalasena S. Effects of zinc supplementation on sexual behavior of male rats. J Hum Reprod Sci 2009 Jul;2(2):57-61.
(27.) Bitran D, Hull EM. Pharmacological analysis of male rat sexual behavior. Neurosci Biobehav Rev 1987;11(4):365-389.
(28.) Culling CF. Miscellaneous staining procedures. In: Lynch's medical laboratory technology. Vol II. 3rd ed. WB Saunders, Philadelphia, USA, 1976.
(29.) Venma PK, Sharma A, Mathur A, Sharma P, Gupta RS, Joshi SC, et al. Effect of Sarcostemma acidum stem extract on spermatogenesis in male albino rats. Asian J Androl 2002 Mar;4(1):43-47.
(30.) Abercrombie M. Estimation of nuclear population from microtome sections. Anat Rec 1946 Feb;94:239-247.
(31.) Das TK, Mazumder R, Biswas NM. Spermatogenesis in rat: effect of L-tryptophan loading. Andrologia 1982 May-Jun;14(3):242-249.
(32.) Das TK, Mazumder R, Biswas NM. Effect of intraventricular injection of 5,6-dihydroxytryptamine on spermatogenesis and plasma testosterone levels in the rat. J Endocrinol 1985 Sep;106(3):395-400.
(33.) Aguilar R, Anton F, Bellido C, Aguilar E, Gaytan F. Testicular serotonin is related to mast cells but not to Leydig cells in the rat. J Endocrinol 1995 Jul;146(1):15-21.
(34.) Campos MB, Vitale ML, Calandra RS, Chiocchio SR. Serotonergic innervation of the rat testis. J Reprod Fertil 1990 Mar;88(2):475-479.
(35.) Tinajero JC, Fabbri A, Dufau ML. Serotonergic inhibition of rat Leydig cell function by propranolol. Endocrinology 1993 Jul;133(1):257-264.
(36.) Sanders-Bush E, Mayer SE. 5-Hydroxytryptamine (Serotonin): Receptor agonists and antagonists. The pharmacological basis of therapeutics. New York, MacGraw-Hill, 2001. pp 269-90.
(37.) Kraeuter Kops S, Theoharides TC, Cronin CT, Kashgarian MG, Askenase PW. Ultrastructural characteristics of rat peritoneal mast cells undergoing differential release ofserotonin without histamine and without degranulation. Cell Tissue Res 1990 Dec;262(3):415-424.
(38.) Das TK, Mazumder R, Biswas NM. Further evidence for an inhibitory effect of L-tryptophan loading on testicular functions of rat. Andrologia 1986 Nov Dec;18(6):618-623.
(39.) Hedger MP, Khatab S, Gonzales G, de Kretser DM. Acute and short-term actions of serotonin administration on the pituitary-testicular axis in the adult rat. Reprod Fertil Dev 1995;7(5):1101-1109.
(40.) Melis MR, Argiolas A. Dopamine and sexual behavior. Neurosci Biobehav Rev 1995;19(1):19-38.
(41.) Gitlin MJ. Psychotropic medications and their effects on sexual function: diagnosis, biology, and treatment approaches. J Clin Psychiatry 1994 Sep;55(9):406-413.
(42.) Shekar S, Satyanarayana S, Kumar KE, Vivek B, Velmurugan C, Kumar BS. Clomipramine affects sexual behavior and reproductive functions in male rats. IJHS 2010 3(3):341-347.
(43.) Brown F, Redfern PH. Studies on the mechanism of action of amantadine. Br J Pharmacol 1976 Dec;58(4):561-567.
(44.) Mercuri NB, Stratta F, Calabresi P, Bernardi G. Nomifensine but not amantadine increases dopamine-induced responses on rat substantia nigra zona compacta neurons. Neurosci Lett 1991 Oct;131(2):145-148.
(45.) Kornhuber J, Weller M. Ama and glutamate hypothesis of schizophrenia experiences in the treatment of neuroleptic malignant syndrome. Journal of Neurotrans. 1993;92(1):57-65.
(46.) Michael D. Griswold. The central role of Sertoli cells in spermatogenesis. Cell & Developmental Biology 1998;9:411-416 .
(47.) McLachlan RI, Wreford NG, O'Donnell L, de Kretser DM, Robertson DM. The endocrine regulation of spermatogenesis: independent roles for testosterone and FSH. J Endocrinol 1996 Jan;148(1):1-9.
(48.) Orth JM. In Cell and Molecular biology of testes: Eds C Desjardin & LL Ewing, Newyork: Oxford University press. 1993; 3-43.
Sheshadri Shekar Devaangam [mail], Vivek B, Velmurugan C, Ashok Kumar
Department of Pharmacology, Sri K.V College of Pharmacy, Chickballapur, Karnataka, India.
Satyanarayana S, Eswar Kumar K
Department of Pharmacy, College of Pharmaceutical Sciences, Visakhapatanam, Andhra Pradesh, India.
Table 1: Effect of chronic oral administration of Amantadine and Clomipramine on sexual behavior parameters of male rats (Data given as mean [+ or -] SEM, N=12 for 0-30th day & N= 6 For 30-60th day). Parameter Control Studied Days 0 15 % Mounted 100 100 % Intromitted 100 100 % Ejaculated 100 100 Mount latency 5.37 [+ or -] 0.84 8.5 [+ or -] 1.29 Intromission 23.5 [+ or -] 4.9 20.65 [+ or -] 4.8 latency Ejaculation 360 [+ or -] 18.4 375.5 [+ or -] 9.4 Latency No of 15.625 [+ or -] 0.3 15.625 [+ or -] 0.3 intromission No of mounts 2.5 [+ or -] 0.32 2.25 [+ or -] 0.36 Post 262.5 [+ or -] 10.9 290 [+ or -] 30.9 ejaculation pause Copulatory 0.85 [+ or -] 0.01 0.86 [+ or -] 0.2 Efficiency Inter 23.13 [+ or -] 1.43 24.15 [+ or -] 0.5 copulatory Interval Parameter Control Studied Days 30 60 % Mounted 100 100 % Intromitted 100 100 % Ejaculated 100 100 Mount latency 8.87 [+ or -] 1.02 7.5 [+ or -] 0.8 Intromission 18.62 [+ or -] 1.4 20.5 [+ or -] 1.8 latency Ejaculation 372.5 [+ or -] 8.8 375 [+ or -] 6.45 Latency No of 15.37 [+ or -] 0.2 15.5 [+ or -] 0.2 intromission No of mounts 2.62 [+ or -] 0.4 3.5 [+ or -] 1.08 Post 225 [+ or -] 15.0 270 [+ or -] 19.14 ejaculation pause Copulatory 0.85 [+ or -] 0.03 0.82 [+ or -] 0.04 Efficiency Inter 24.29 [+ or -] 0.8 24.2 [+ or -] 0.7 copulatory Interval Parameter AMA + CLMP 13.5 mg/kg Studied Days 0 15 % Mounted 100 100 % Intromitted 100 100 % Ejaculated 100 75 Mount latency 4.57 [+ or -] 0.32 70 [+ or -] 5.3 ** Intromission 177.5 [+ or -] 18.7 ** 190.5 [+ or -] 30.5 ** latency Ejaculation 430 [+ or -] 21.95 * 945 [+ or -] 196.6 ** Latency No of 17.12 [+ or -] 0.44 * 24.8 [+ or -] 1.77 ** intromission No of mounts 3.5 [+ or -] 0.42 4.12 [+ or -] 0.4 * Post 335.5 [+ or -] 32.5 * 632.5 [+ or -] 248 * ejaculation pause Copulatory 0.79 [+ or -] 0.16 0.8 [+ or -] 0.02 Efficiency Inter 21.44 [+ or -] 3.4 38.3 [+ or -] 7.4 copulatory Interval Parameter AMA + CLMP 13.5 mg/kg Studied Days 30 60 % Mounted 100 100 % Intromitted 100 50 % Ejaculated 75 50 Mount latency 69.75 [+ or -] 5.1 ** 115 [+ or -] 2.88 * Intromission 237.5 [+ or -] 13.3 ** 672.5 [+ or -] 376.3 * latency Ejaculation 832.5 [+ or -] 211.6 ** 1452.5 [+ or -] 200.7 * Latency No of 23.5 [+ or -] 0.5 ** 13.75 [+ or -] 6.8 * intromission No of mounts 3.8 [+ or -] 0.47 8.25 [+ or -] 0.7 * Post 667.5 [+ or -] 248.0 * 1105 [+ or -] 401.7 * ejaculation pause Copulatory 0.86 [+ or -] 0.01 0.49 [+ or -] 0.22 Efficiency Inter 35.58 [+ or -] 8.1 35.3 [+ or -] 20. 3 copulatory Interval Parameter AMA + CLMP 27 mg/kg Studied Days 0 15 % Mounted 100 100 % Intromitted 100 75 % Ejaculated 75 50 Mount latency 10.75 [+ or -] 0.5 ** 71.8 [+ or -] 4.8 ** Intromission 637.5 [+ or -] 254.0 ** 1058.75 [+ or -] 280.23 ** latency Ejaculation 817.5 [+ or -] 215.12 ** 1395 [+ or -] 154.95 ** Latency No of 16.3 [+ or -] 3.9 9 [+ or -] 3.4 ** intromission No of mounts 3.75 [+ or -] 0.5 6.3 [+ or -] 0.4 ** Post 615 [+ or -] 258.7 * 1137.5 [+ or -] 250.6 ** ejaculation pause Copulatory 0.61 [+ or -] 0.13 0.35 [+ or -] 0.13 ** Efficiency Inter 18.2 [+ or -] 4.8 39.03 [+ or -] 17.15 copulatory Interval Parameter AMA + CLMP 27 mg/kg Studied Days 30 60 % Mounted 100 100 % Intromitted 75 50 % Ejaculated 25 0 Mount latency 127.5 [+ or -] 12.7 ** 248.7 [+ or -] 52.4 * Intromission 1113.7 [+ or -] 259.5 ** 1165 [+ or -] 366.6 * latency Ejaculation 1597.5 [+ or -] 133.6 ** 1800 [+ or -] 0 * Latency No of 8.5 [+ or -] 3.4 ** 5 [+ or -] 3 * intromission No of mounts 12.5 [+ or -] 1.2 ** 10 [+ or -] 1.8 * Post 1462.5 [+ or -] 221.15 ** 1800 [+ or -] 0 * ejaculation pause Copulatory 0.61 [+ or -] 0.13 0.35 [+ or -] 0.13 ** Efficiency Inter 18.2 [+ or -] 4.8 39.03 [+ or -] 17.15 copulatory Interval Parameter AMA + CLMP 54 mg/kg Studied Days 0 15 % Mounted 100 100 % Intromitted 100 50 % Ejaculated 41.6 25 Mount latency 33.12 [+ or -] 0.98 ** 115 [+ or -] 7.3 ** Intromission 245 [+ or -] 14.01 ** 1017.5 [+ or -] 295.9 ** latency Ejaculation 1382.5 [+ or -] 207.35 * 1560 [+ or -] 163.5 ** Latency No of 17.75 [+ or -] 3.0 7.75 [+ or -] 2.9 ** intromission No of mounts 4.8 [+ or -] 0.9 7.6 [+ or -] 1.05 ** Post 1237.5 [+ or -] 274.7 ** 1475 [+ or -] 212.7 ** ejaculation pause Copulatory 0.61 [+ or -] 0.13 0.35 [+ or -] 0.13 ** Efficiency Inter 18.2 [+ or -] 4.8 39.03 [+ or -] 17.15 copulatory Interval Parameter AMA + CLMP 54 mg/kg Studied Days 30 60 % Mounted 100 0 % Intromitted 41.6 0 % Ejaculated 0 0 Mount latency 262.5 [+ or -] 20.15 ** 1800 [+ or -] 0 * Intromission 1220 [+ or -] 283.27 ** 1800 [+ or -] 0 * latency Ejaculation 1800 [+ or -] 0 ** 1800 [+ or -] 0 * Latency No of 6 [+ or -] 2.9 ** 0 * intromission No of mounts 5.8 [+ or -] 1.1 0 * Post 1800 [+ or -] 0 ** 1800 [+ or -] 0 * ejaculation pause Copulatory 0.61 [+ or -] 0.13 0.35 [+ or -] 0.13 ** Efficiency Inter 18.2 [+ or -] 4.8 39.03 [+ or -] 17.15 copulatory Interval Significant atp values: <0.0S *, 0.01 ** compared to control (Mann- Whitney "U" Test) Table 2: Influence of Amantadine and Clomipramine on serum testosterone levels in male rats (Data given as mean [+ or -] SEM, N=6). Treatment Testosterone ng/ml Testosterone ng/ml (30 DAYS) (60 DAYS) Control 1 ml/kg 6.55 [+ or -] 0.66 5.07 [+ or -] 0.3 AMA + CLMP 5.68 [+ or -] 0.6 5.77 [+ or -] 0.45 13.5 mg/kg AMA + CLMP 3.8 [+ or -] 0.51 ** 2.97 [+ or -] 0.17 ** 27 mg/kg AMA + CLMP 1.95 [+ or -] 0.14 ** 1.5 [+ or -] 0.04 ** 54 mg/kg Significant at p < 0.05 *, 0.01 ** compared to control (student "t" test) Table 3: Amantadine and Clomipramine treatment influence on histology of testes (Data given as mean [+ or -] SEM, N=6). Treatment Sertoli Cells (days) 30 Days 60 Days Control 3.5 [+ or -] 0.288 3.5 [+ or -] 0.288 1 ml/kg AMA + CLMP 2.75 [+ or -] 0.25 3 [+ or -] 0.4 13.5 mg/kg AMA + CLMP 2.75 [+ or -] 0.2 2.25 [+ or -] 0.2 ** 27 mg/kg AMA + CLMP 1.5 [+ or -] 0.2 ** 1.5 [+ or -] 0.2 ** 54 mg/kg Treatment Sp gonia (days) 30 Days 60 Days Control 8.25 [+ or -] 0.4 8.25 [+ or -] 0.4 1 ml/kg AMA + CLMP 7 [+ or -] 0.48 6.5 [+ or -] 0.28 ** 13.5 mg/kg AMA + CLMP 5 [+ or -] 0.4 ** 5 [+ or -] 0.7 ** 27 mg/kg AMA + CLMP 4 [+ or -] 0.40 ** 4.5 [+ or -] 0.29 ** 54 mg/kg Treatment Secondary Spermotocytes (days) 30 Days 60 Days Control 48.75 [+ or -] 0.75 48.75 [+ or -] 0.75 1 ml/kg AMA + CLMP 49.75 [+ or -] 0.9 49.25 [+ or -] 2 13.5 mg/kg AMA + CLMP 35.5 [+ or -] 1.56 ** 29.5 [+ or -] 0.86 ** 27 mg/kg AMA + CLMP 25.75 [+ or -] 0.8 ** 22 [+ or -] 0.5 ** 54 mg/kg Treatment Spermatids (days) 30 Days 60 Days Control 119.75 [+ or -] 2.04 113.8 [+ or -] 2.24 1 ml/kg AMA + CLMP 65.125 [+ or -] 1.74 *** 65.12 [+ or -] 1.73 *** 13.5 mg/kg AMA + CLMP 48.125 [+ or -] 1.30 *** 39.75 [+ or -] 1.6 *** 27 mg/kg AMA + CLMP 26.37 [+ or -] 1.54 *** 15.87 [+ or -] 1.34 *** 54 mg/kg Significant at p <0.05 *, 0.01 ** compared to control (student "t" test)
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|Title Annotation:||Original Article|
|Author:||Devaangam, Sheshadri Shekar; Satyanarayana, S.; Kumar, K., Eswar; Vivek, B.; Velmurugan, C.; Kumar,|
|Publication:||Oman Medical Journal|
|Date:||Nov 1, 2011|
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