An investigation into the effects and possible mechanisms of action of cimetidine and ranitidine on the sexual behaviour of male rats.

Abstract

The development of a new class of antihistamines, the

H2-receptor antagonists, introduced a new era in the

treatment of peptic ulcer diseases. Cimetidine, the first

clinically effective H2-blocker, was introduced in 1976.

Recently ranitidine, a second member approved for clinical

use, has been found to be as effective as cimetidine in

the management of peptic ulcer diseases. Soon after the

introduction of cimetidine several reports of loss of

libido, impotence and gynaecomastia were described in male

patients who were on normal or high therapeutic doses of

cimetidine. A few unsubstantiated reports of loss of

libido and gynaecomastia attributed to ranitidine therapy

have also appeared in literature.

This study was undertaken to examine in detail the effects

of acute and subchronic treatment with cimetidine and

ranitidine on mating behaviour in sexually active male

rats. Motor activity counts were recorded immediately

before sexual behaviour observations. The animals were

tested on every third day and observations were terminated

after the first intromission of the next series of

copulations. In the single dose study, mating behaviour

tests were commenced 2 hours after treatment; mating tests

during the subchronic dose studies were done 4 to 7 hours

after the 6hOO dose. The following measures were used in

the analysis of data: mount latency, intromission latency,

mount frequency, intromission frequency, ejaculation

latency, and the postejaculatory intromission latency. At

the termination of the subchronic dose studies blood

samples were collected by cardiac puncture and the animals

were subsequently autopsied. Cauda epididymal sperm counts

and motility were determined, testes and accessory sex

organs were weighed, and one testis was processed for

histological examination.

Cimetidine in the low dose, 128.6 mg/kg, significantly

shortened the ejaculatory latency and to a lesser extent

the postejaculatory intromission latency. At the higher

dose, 257.1 mg/kg, cimetidine markedly prolonged the

postejaculatory intromission latency and to a lesser

extent increased the ejaculation latency. The inhibitory

effect of cimetidine on copulatory behaviour at the higher

dose level was accompanied by significant depression in

motor activity.

At the conclusion of the subchronic dose studies marked

reductions in serum testosterone levels and decreased

testes and accessory organ weights were observed in the

cimetidine group. No significant changes in sperm counts

were observed, although the sperm counts in the cimetidine

group were lower than the control values. Histological

examination of testes showed apparently normal

spermatogenesis in all three treatment groups.

However, in spite of the reduced testosterone levels and

decreased testes and accessory sex organ weights in the

cimetidine group, no impairment in mating behaviour was

observed.

In both the acute and the subchronic dose studies, similar

to placebo, treatment with ranitidine showed no effect on

mating behaviour.

On final analysis of the results it is concluded that

cimetidine, and not ranitidine, disrupts sexual behaviour

in male rats. Furthermore, it is concluded that the effect

of cimetidine on sexual behaviour is not related to

H2-receptor blockade as equipotent doses of ranitidine did

not produce similar effects. The mechanism of

cimetidine-induced impairment of sexual performance in the

male rat may possibly be attributed to some non-specific,

direct or indirect action of cimetidine on some

neurotransmitter system responsible for the control of

sexual behaviour. It is further suggested that the effect

may possibly be mediated by a blockade of central dopamine

receptors. However, it must be stressed that further

experimentation is necessary to elucidate the mechanism of

action of cimetidine on sexual behaviour.